research - Instituto de Neurobiología
Transcription
research - Instituto de Neurobiología
1 Dr. Juan Ramón de la Fuente Rector Lic. Enrique del Val Blanco General Secretary Mtro. Daniel Barrera Pérez Administrative Secretary Dra. Rosaura Ruiz Gutiérrez Secretary of Institutional Development Mtro. José Antonio Vela Capdevila Secretary of Community Services Mtro. Jorge Islas López General Attorney Dr. René R. Drucker Colín Coordinator of Scientific Research Dr. Carlos Arámburo de la Hoz Director of the Institute of Neurobiology Copyright 2005 © Institute of Neurobiology UNAM Juriquilla Campus Design Mariana Larrañaga mldiseno@terra.com.mx Photography Laura Sánchez Printed in México 2 All rights reserved. No portion of this publicatim may be reproduced, stored in a retrieval system, or transmitted in any form or by any means,electronic, mechanical, photocopying, recording or otherwise without permission of the Institute of Neurobiology.. INDEX Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Department of Cellular and Molecular Neurobiology . . . . . . . . . . . . . . . . . 3 Carmen Aceves, Ph.D. Energy Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Carlos Arámburo, Ph.D. Hormone Biochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Rogelio Arellano, Ph.D. Cellular Neurophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Carmen Clapp, Ph.D. Molecular Endocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Mauricio Díaz-Muñoz, Ph.D. Cell Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Jesús García-Colunga, Ph.D. Molecular Neurobiology I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Edgar P.Heimer, Ph.D. Marine Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Gonzalo Martínez de la Escalera, Ph.D. Reproductive Neuroendocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Ataúlfo Martínez-Torres, Ph.D. Molecular Neurobiology II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Flavio Mena, Ph.D. Physiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Ricardo Miledi, Ph.D. Molecular Neurobiology I & II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Teresa Morales, Ph.D. Functional Neuroanatomy of the Hypothalamus . . . . . . . . . . . . . . . . . . . 16 Carlos Valverde-R, M.D. Evolutive Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Department of Developmental Neurobiology and Neurophysiology. . . . . 19 Alfonso Cárabez-Trejo, Ph.D. Neuromorphotoxicology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 León Cintra, Ph.D. Cronobiology and EEG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Miguel Condés-Lara, Ph.D. Pain and Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Sofía Díaz, Ph.D. Neuromorphometry and Development . . . . . . . . . . . . . . . . . . . . . . . . . . 24 3 Jorge Larriva-Sahd, Ph.D. Neuromorphology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Juan Riesgo-Escovar, Ph.D. Molecular Signal Transduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Manuel Salas, Ph.D. Neurophysiology and Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Alfredo Varela-Echavarría, Ph.D. Neural Diferentiation and Axogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Department of Behavioral and Cognitive Neurobiology . . . . . . . . . . . . . . 29 Fernando Barrios, Ph.D. Brain Mapping.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Antonio Fernández-Bouzas, Ph.D. Psychophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Thalía Fernández, Ph.D. Neurofeedback . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Magda Giordano, Ph.D. Brain Plasticity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Thalía Harmony, Ph.D. Psychophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Hugo Merchant, Ph.D. Neurophysiology of Perception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Isabel Miranda, Ph.D. Neuropharmacology of Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Raúl Paredes, Ph.D. Sexual Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Roberto Prado-Alcalá, Ph.D. Neurobiology of Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Gina Quirarte, Ph.D. Neurobiology of Learning. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Victor Ramírez-Amaya, Ph.D. Plastic Neural Networks and Cognition . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Graduate Programs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Neurodevelopment Research Unit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Research Core Facilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Academic Services Units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 The INB in numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Locations of National Autonomous University of Mexico Campi . . . . . . . . 64 Queretaro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Directory 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 PRESENTATION The current Institute of Neurobiology (INB) is a heir of the Mexican school of research on integrative neurobiology, which originated in the 1940´s when diverse groups from various institutions dispersed throughout the country started to work on neurophysiology, experimental neuropsychiatry, psychophysiology, behaviour, neuroanatomy, neurochemistry, and neuroendocrinology. Notwithstanding the long-established Mexican tradition of neuroscience studies, a university-based institute, devoted mainly to research on the nervous system and its functions did not exist. Therefore, in 1993 the National Autonomous University of Mexico (Universidad Nacional Autónoma de México, UNAM) decided to support the consolidation of this area by creating an institution that not only acknowledged the inveteracy of such a discipline in the country but, even more importantly, also promoted the education and training of students in this area. This decision was strengthened by the explosive development of the neurosciences at an international level, pumped by the so-called “Brain Decade” (1990-2000) and by the commitment to promote integrative studies of the structure, mechanisms of operation, and function of the nervous system using multi-, inter-, and transdisciplinary approaches. Simultaneously, it was considered desirable to broaden the decentralization process of the University system of scientific research, locating this Institute in a new campus, Juriquilla, in the State of Queretaro. This would foster the formation of a new pole of academic development in the Bajio region (situated in the central part of Mexico) that would strengthen the national character of UNAM. This booklet gives an account of the mission, structure, and aims –research, teaching, creation of collaboration, and outreach– of the Institute of Neurobiology. It also shows briefly the graduate programs, human resources, diverse lines of research pursued in its laboratories, and infrastructure. With these elements, INB takes up the challenge of contributing, in the beginning of the third millennium, to unravel some of the mysteries guarded by this marvellous organ constituting our internal universe: the brain. Carlos Arámburo Ph.D Director aramburo@servidor.unam.mx 1 OBJECTIVES The main objective of the Institute of Neurobiology (INB) is to generate original knowledge in the field of neurosciences; study of the brain is one of the most thrilling and promising scientific endeavors of our times, is essential for a better understanding of the functioning of the nervous system, human nature, and diverse neurological and psychiatric diseases. The INB undertakes research on the structure and function of the brain with a multidisciplinary approach by focusing its attention at different levels: molecular, cellular, tissue, organ, behavioral, and cognitive, and by using analytical and integrative models. In addition, research lines with a clinical perspective have been incorporated. The institute wants to encourage a fruitful interaction among the research groups by taking advantage of the diversity of subjects and competencies in traditionally divergent areas such as biological science, behavioral science, bioinformatics, and humanities. Of equal relevance for the INB is the training of high-level human resources, at both the undergraduate and graduate levels, in order to strengthen the academic and health sectors in their respective areas of competence. In addition, this institution contributes importantly to the decentralization of scientific activities in Mexico by promoting, with other units within the Juriquilla Campus, a first--level pole of scientific development in the central region of the country. RESEARCH The Institute of Neurobiology integrates a wide platform of multidisciplinary research on neurosciences, distributed along three main fundamental axes, viz: a) A multi-level approach that ranges from molecular and cellular aspects, going through tissues, organs, and systems to reach the emergent properties of nervous activity such as behavior and cognition; b) These aspects are studied through the development of an organism as a whole, starting from the embryonic stage to maturity and senescence, and c) Various influences are considered that may be genetic or epigenetic, as well as their consequences at physiological and pathological levels. 2 Research activities take place in laboratories organized in three departments: • Department of Cellular and Molecular Neurobiology • Department of Developmental Neurobiology and Neurophysiology • Department of Behavioral and Cognitive Neurobiology In this department various neurobiological processes are studied ranging from basic and fundamental mechanisms of neural communication –chemical and electrical– to processes underlying clinical, pharmacological, and zootechnical manifestations. Multidisciplinary projects include molecular and functional characterization of ionic channels, as well as characterization of receptors, and signaling pathways involved in neurotransmission and neurosecretion; and also the study of the structural and biological diversity of various neuroendocrine messengers, employing comparative approaches throughout evolution, and characterization of novel neuroactive compounds of marine origin. In addition, research is performed on the regulatory mechanisms of complex processes such as reproduction, lactation, stress, growth, metabolism, and angiogenesis, and pathological processes such as cancer. PRINCIPAL INVESTIGATORS Carmen Aceves Carlos Arámburo Rogelio Arellano Carmen Clapp Mauricio Díaz-Muñoz Jesús García-Colunga Edgar P. Heimer Gonzalo Martínez de la Escalera Ataulfo Martínez-Torres Flavio Mena Ricardo Miledi Teresa Morales Carlos Valverde-R 4 THYRONINE DEIODINATION IN THE DIFFERENTIATION OF NORMAL AND PATHOLOGICAL MAMMARY TISSUE Carmen Aceves, Ph.D. Associate Professor caracev@servidor.unam.mx Ph.D. in Physiology, National University of Mexico, Mexico, 1988. Postdoctoral Fellow, Dartmouth College, New Hampshire, USA, 1994 Our goal is to understand the role played by local production of triiodothyronine (T3) and iodine in the histological and functional differentiation of the mammary gland. We found that this local production called deiodination, shows changes in specific activity and distribution within the mammary tissue during pregnancy and lactation that are related both to differentiation and to metabolic adjustments in mammary tissue required to sustain milk production. During lactation, the suckling stimulus and sympathetic innervation modulate these adjustments. The mammary deiodination also generates high concentrations of free iodine that contribute to the iodine pool in the milk and may participate in the redox equilibrium of the epithelial cell. In this regard, recent reports show that iodine is a potent natural antioxidant that neutralizes free radicals, which have been thought to be a major factor responsible for cancer promotion. Our current work includes animal models of normal mammary tissue development and pharmacologically induced mammary cancer. We are analyzing specific modifications in genes related to both normal and neoplastic cell transformation, and by modulating deiodination, we are trying to gain a better understanding of the early intracellular processes that accompany carcinogenesis. RELEVANT PUBLICATIONS: Anguiano B, Rojas-Huidobro R, Delgado G, Aceves C. Has the mammary gland a protective mechanism against overexposure to T3 during the peripartum period?. The prolactin pulse down- regulates mammary type I deiodinase responsiveness to norepinephrine. Journal of Endocrinology 183: 273-276, 2004. Garcia-Solis P, Aceves C. 5’Deiodinase in two breast cancer cell lines: effect of triiodothyronine, isoproterenol and retinoids. Molecular and Cellular Endocrinology 201: 25-32, 2003. Aceves C, Rojas-Huidobro R. Effect of suckling and sympathetic nervous system on peripheral deiodination in the lactating rat. Journal of Endocrinology 171: 533-540, 2001. Aceves C, Pineda O, Ramirez-C I, Navarro L, Valverde-R C. Mammary type I deiodinase is dependent on the suckling stimulus. Differential role of norepinephrine and prolactin. Endocrinology 140: 2948-2950, 1999. Navarro L, Landa A, Valverde-R C, Aceves C. Mammary 5´deiodinase type I is encoded by a short messenger. Endocrinology 138: 4248-4254, 1997. . Group members: Brenda Anguiano, Ph.D. Research Associate Ma. Guadalupe Delgado, B.Sc. Technician 5 CHARACTERIZATION OF THE MOLECULAR AND FUNCTIONAL HETEROGENEITY OF GROWTH HORMONE (GH) Carlos Arámburo, Ph.D. RELEVANT PUBLICATIONS: Harvey S, Baudet M-L, Murphy AE, Luna M, Hull KL, and Arámburo C. Testicular growth hormone (GH): GH expression in spermatogonia and primary spermatocytes. General and Comparative Endocrinology 139: 158167, 2004. Luna MM, Huerta L, Berumen L, MartínezCoria H, Harvey S, Arámburo C. Growth hormone (GH) in the male reproductive tract: heterogeneity and changes during ontogeny and maturation. General and Comparative Endocrinology 137: 37-49, 2004. Martínez-Coria H, López-Rosales LJ, Carranza M, Berumen L, Luna M, Arámburo C. Differential secretion of chicken growth hormone variants after GHRH stimulation, in vitro. Endocrine 17: 91-102, 2002. Arámburo C, Carranza M, Reyes M, Luna M, Martínez-Coria H, Berumen L, Scanes CG. Characterization of a bioactive 15 kDa fragment produced by proteolytic cleavage of chicken growth hormone. Endocrine 15: 231-240, 2001. Arámburo C, Luna M, Carranza M, Reyes M, Martínez-Coria H, Scanes CG. Growth hormone size variants: changes in the pituitary during development of the chicken. Proceedings of the Society for Experimental Biology and Medicine 223: 67-74, 2000. Group members: Maricela Luna, Ph.D. Assistant Professor 6 Martha Carranza, M.Sc. Technician Associate Professor aramburo@servidor.unam.mx Ph.D. in Chemical Sciences (Biochemistry), National University of Mexico, Mexico, 1983. Postdoctoral Fellow, Rutgers-The State University of New Jersey, USA. 1985. Most pituitary hormones are structurally heterogeneous and also show wide functional diversity. The interest of this group is focused on characterizing growth hormone heterogeneity and establishing a correlation between the structural variants of GH and its multiple functions. We have shown that GH is actually a family of proteins whose members differ from each other in their basic structure due to a number of chemical modifications (such as glycosylation, phosphorylation, proteolytic cleavage, or oligomerization) or because they are generated by alternative splicing. Some of the molecular variants of GH seem to influence diverse aspects of metabolism pathways by means of specific biological activities that are not shared by all members of this hormone family. The pattern of molecular heterogeneity observed in the pituitary is maintained in plasma, which strongly suggests that the variants are effectively released into the circulation. We have also shown that the synthesis and/or secretion of pituitary GH variants are subject to differential regulation, since their relative concentrations change during growth and development and under different physiological and experimental conditions. In addition, we are studying the presence and distribution of GH in extrapituitary tissues, such as the reproductive apparatus, the immune system, the eye and the brain. We have analyzed the expression of GH mRNA, quantified the amount of GH protein and studied its pattern of molecular heterogeneity in these tissues and compared it with that found in the pituitary. We have also described some of the cells of the extrapituitary tissues where GH is found. Based on these findings we suggest that GH plays a paracrine and/or autocrine role in such tissues. The experimental approaches employed in these studies are supported by methodologies that involve protein biochemistry, molecular biology, tissue and cell culture, quantitative and qualitative immunotechniques, as well as in vitro and in vivo bioassays. . CELLULAR AND MOLECULAR PHYSIOLOGY OF CELL COMMUNICATION Rogelio Arellano, Ph.D. Assistant Professor arellano@inb.unam.mx Ph.D. in Physiology. Centro de Investigación y de Estudios Avanzados, México D.F., 1990 Postdoctoral Fellow, California University, Irvine, CA, USA, 1990-1995. The principal goal of studies in this laboratory is to understand the systems of intercellular communication during different complex physiological processes. Distinct cellular and molecular aspects of these processes are studied using modern techniques and concepts from electrophysiology and molecular and cell biology. Our research uses cellular models for folliculogenesis and neuronglia communication, which represent important paradigms for the study of cellular interactions. The importance of intercellular communication in folliculogenesis is evident due to the interdependence between the different cellular components of the follicle that communicate via chemical and electrical signaling mechanisms, both of which are fundamental for the proper development of the gamete. In order to learn more about these pathways we are studying follicles from Xenopus and from different mammals. Communication between neurons and glia is important for proper operation of the nervous system, and their multiple interactions have a role in essential neuronal functions, such as action potential propagation, chemical signaling, and plasticity. In order to elucidate these interactions, we study signaling mechanisms in the mammalian optic nerve and in cultured oligodendrocytes. Our goal is to describe and analyze the different communication pathways in these models, from the molecular elements involved, to the physiological consequences of their activation. For this, our work is focused on the role of purinergic communication, a pathway that is stimulated by transmitters used by different cells, and is fundamental in several physiological processes. RELEVANT PUBLICATIONS: Saldaña C, Vázquez F, Garay E, Arellano RO. Epithelium and/or theca are required for ATP-elicited K+ current in follicle-enclosed Xenopus oocytes. Journal of Cellular Physiology 202:814-821,2005. Arellano RO, Martinez-Torres A, Garay E. Ionic currents activated via purinergic receptors in the cumulus cell-enclosed mouse oocyte. Biology of Reproduction 67: 837846, 2002. Arellano RO, Garay E, Miledi R. Muscarinic receptor heterogeneity in follicle-enclosed Xenopus oocytes. Journal of Physiology (London) 521: 409-419, 1999. Arellano RO, Garay E, Miledi R. Cl- currents activated via purinergic receptors in Xenopus follicles. American Journal of Physiology 274 Cell Physiol. 43:C333-C340, 1998. Arellano RO, Woodward RM, Miledi R. A monovalent cationic conductance that is blocked by extracellular divalent cations in Xenopus oocytes. (London) 484: 593-604, 1995. Group members: Carlos Saldaña, Ph.D. Research Associate T. Edith Garay, Ph.D. Technician 7 HORMONAL REGULATION OF ANGIOGENESIS AND VASCULAR FUNCTION Carmen Clapp, Ph.D. RELEVANT PUBLICATIONS: Dueñas Z, Rivera JC, Quiróz-Mercado H, Aranda J, Macotela Y, Montes de Oca P, López-Barrera F, Nava G, Guerrero JL, Suárez A, De Regil M, Martínez de la Escalera G, Clapp C. Prolactin in the eye of patients with retinopathy of prematurity: implications for vascular regression. Investigative Ophthalmology & Visual Science 45: 2049-2055, 2004. Corbacho AM, Martínez de la Escalera G, Clapp C. Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis. Journal of Endocrinology 173: 219-238, 2002. Corbacho AM, Nava G, Eiserich JP, Noris G, Macotela Y, Struman I, Martínez de la Escalera G, Freeman BA, Clapp C. Proteolytic cleavage confers nitric oxide synthase inducting activity upon prolactin. Journal of Biological Chemistry 275: 13183-13186, 2000. Dueñas Z, Torner L, Corbacho A, Ochoa A, Gutiérrez-Ospina G, Barrios F, Berger P, Martínez de la Escalera G, Clapp C. Inhibition of rat corneal angiogenesis by 16kDa prolactin and endogenous prolactin-like molecules. Investigative Ophthalmology & Visual Science 40: 2498-2505, 1999. Clapp C, Torner L, Gutiérrez-Ospina G, Alcántara E, López-Gómez F, Nagano M, Kelly PA, Mejia S, Morales M, Martínez de la Escalera G. Prolactin gene is expressed in the hypothalamo-neurohypophyseal system and the protein is processed into a 14 kDa fragment with 16K prolactin-like activity. Proceedings of the National Academy of Sciences, USA 91: 10384-10388, 1994. . Group members: Carmen González, Ph.D. Research Associate 8 Fernando López, M. Sc. Technician Professor clapp@servidor.unam.mx Ph.D. Physiology, National University of Mexico, Mexico, 1984. Posdoctoral Fellow, University of California, Berkeley, CA., USA, 1985-1988. We study the hormone prolactin, from its molecular structure to its functions. We address the fact that specific proteolytic cleavage transforms prolactin into a potent inhibitor of the neo-formation of blood vessels that also has stimulatory effects on vascular tone and inflammation. We investigate the endogenous generation of prolactin fragments in normal and diseased states, their unique functional properties, the regulation of the specific proteases, and the expression of relevant receptors and associated signaling pathways. Understanding these molecules opens new perspectives on the functional link between angiogenesis, vascular function, inflammation, and well-recognized, gender-specific, and reproduction-related hormonal effects. Moreover, this information should contribute to new therapeutic approaches to control pathologies characterized by inflammation and exacerbated angiogenesis, such as rheumatoid arthritis, diabetic retinopathy, and tumor neovascularization. CELLULAR PHYSIOLOGY OF INTRACELLULAR CALCIUM DYNAMICS AND REGULATION OF THE FOOD ENTRAINED OSCILLATOR Mauricio Díaz-Muñoz, Ph.D. Professor mdiaz@servidor.unam.mx Ph.D. in Basic Biomedical Research, National University of Mexico, Mexico, 1990. Posdoctoral Fellow, Baylor College of Medicine, Houston, TX, 1990-1991; University of California in San Diego, USA, 1992-1993. There are two principal fields of interest in our research: 1) Regulation of the elements involved in the dynamics of intracellular calcium, and 2) Biochemical and physiological adaptations in the liver during the expression of the food entrained oscillator. The current projects in the first area are: • Modulation of the ryanodine recpetor by adenosine and its metabolites • Role of the ryanodine and IP3 receptors in the plateau potentials and wind up in turtle spinal motor neurons • Alteration of the cardiac sarcoplasmic reticulum in an experimental model of heart failure • Characterization of the ryanodine and IP3 receptors, and thapsigarginsensitive Ca2+ ATPase in the fruit fly, Drosophila melanogaster The current projects in the second area are: • Adaptations of hepatic mitochondrial metabolism in food restricted rats • Changes in nitrogen metabolism during the expression of the food entrained oscillator • Stereological changes in hepatocytes during food restriction • Modulation of the liver thyroidal state in rats under restricted feeding RELEVANT PUBLICATIONS: Morales-Tlalpan V, Arellano RO, Díaz-Muñoz M. Interplay between ryanodine and IP3 receptors in ATP-stimulated luteinized-granulosa cells. Cell Calcium 37:203-213, 2005. Báez-Ruiz A, Vázquez-Martínez O, Ramírez J, Díaz-Muñoz M. The food entrainable oscillator studied by DNA microarrays: What is the liver doing during food anticipatory activity. Biological Rhythm Research (In press). 2004. Ángeles-Castellano M, Mendoza J, Díaz-Muñoz M, Escobar C. Food entrainment modifies the c-FOS expressión in the brain stem of the rats. American Journal of Physiology En prensa. 286:R158-R165,2005. Vázquez-Martínez O, Cañedo-Merino R, Díaz-Muñoz M, Riesgo-Escovar J. Biochemical, anatomical and phylogenetic characterization of the ryanodine and IP3 receptors and thapsigargin-sensitive Ca2+ ATPase in Drosophila melanogaster. Journal of Cell Science 116: 2483-2494, 2003. Butanda-Ochoa A, Hoger G, Díaz-Muñoz M. Modulation of calcium release channel/ ryanodine receptor from sarcoplasmic reticulum by adenosine and its metabolites. A structure-function approach. Bioorganic and Medicinal Chemistry 11: 3029-3037, 2003. Group members: Verónica Morales, Ph.D. Research Associate Olivia Vázquez, B.Sc. Technician 9 MODULATION OF MUSCLE AND NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS BY EXOGENOUS AND/OR ENDOGENOUS COMPOUNDS Jesús García-Colunga, Ph.D. RELEVANT PUBLICATIONS: García-Colunga J, González-Herrera M, Miledi R. Modulation of nicotinic acetylcholine receptors by zinc. Neuroreport 12: 147-150, 2001. López-Valdés H, García-Colunga J. Antagonism of nicotinic acetylcholine receptors by inhibitors of serotonin uptake. Molecular Psychiatry 6: 511-519, 2001. García-Colunga J, Awad JN, Miledi R. Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (prozac).Proceedings of the National Academy of Sciences USA 94: 2041-2044, 1997. García-Colunga J, Miledi R. Serotonergic modulation of muscle acetylcholine receptors of different subunit composition. Proceedings of the National Academy of Sciences USA 93: 3990-3994, 1996. García-Colunga J, Miledi R. Effects of serotonergic agents on neuronal nicotinic acetylcholine receptors. Proceedings of the National Academy of Sciences USA 92: 2919-2923, 1995. 10 Assistant Professor garciac@inb.unam.mx Ph.D. in Physiology, Centro de Investigación y de Estudios Avanzados, México, 1991. Posdoctoral Fellow, University of California, Irvine, CA, USA, 1992-1996. Nicotinic acetylcholine receptors are cationic channels opened by binding of the neurotransmitter acetylcholine. These receptors are membrane proteins and are the key to nicotinic cholinergic transmission at the neuromuscular junction, as well as in different regions of the peripheral and central nervous systems. However, their functional significance in the nervous system is not well understood. The function of nicotinic receptors is modified by a wide variety of endogenous substances and ions including serotonin, substance P, Ca2+, Mg2+ and Zn2+. We are interested in studying, from cellular and molecular points of view, the modulation of neuronal nicotinic receptors by serotonergic compounds, such as agonists and antagonists of serotonin receptors and monoamine reuptake inhibitors, some of which are used clinically to treat mental depression. We are focusing on establishing the specific targets of these substances and the mechanistic details of their interactions with neuronal nicotinic receptors. The results of these studies raise the possibility that the nicotinic receptors of the brain may be sites where therapeutic antidepressants act. Thus, they may play an important role in designing new antidepressants for clinical medicine. We are also investigating functional neurotransmitter receptors and voltagegated ion channels located in glial cells. Recently, we are studying responses to serotonin and angiotensin II, as well as voltage-gated potassium currents. MARINE NEUROPHARMACOLOGY: PURIFICATION, CHARACTERIZATION AND EVALUATION OF NEUROACTIVE PEPTIDES AND PROTEINS FROM MARINE INVERTEBRATES Edgar P. Heimer, Ph.D. Professor heimer@servidor.unam.mx Ph.D. (Sciences), Columbia University, 1965 Industrial Career: Research Department, Hoffmann-La Roche, Nutley, NJ, 1965-1994. One of our research areas involves the study of venomous marine invertebrates belonging to the Phylum Cnidaria. Our focus is primarily on the medusas and fire corals found in the Mexican Caribbean whose stings cause pain, pruritus, inflammation and are a hazard to swimmers in this touristic area. The toxins of these organisms are composed of a number of polypeptides and proteins and our efforts have been directed towards their chemistry, toxicology, immunology and treatment of their stings. We are also involved in the evaluation of compounds isolated from predatory marine snails belonging to the Order Neogastropoda which interact with receptors and modulate ionic channel function in both invertebrates and vertebrates. These peptides have a potent, high affinity interactions with their targets that have permitted their use as tools for the further undestanding of cellular communication. We have demonstrated that worm eating members of the Superfamily Conacea (conus and turrids) possess at least 3 new types of biologically active peptides (Conorfamide, agonist of nicotinic acid receptors and “Turritoxins”) in their venoms. As a result of these findings, we have extended our work as to include other members of this order which have been reported to have the capacity to paralyze their prey. Our studies also include zoogeographical and taxonomic (classical and molecular) aspects. RELEVANT PUBLICATIONS: Pless DD, Aguilar MB, Falcón A, Lozano E, Heimer de la Cotera E. Latent phenoloxidase activity and N-terminal amino acid sequence of hemocyanin from Bathynomus giganteus, a primitive crustacean. Archives of Biochemistry and Biophysics 409: 402410, 2003. Rojas A, Torres M, Rojas JI, Feregrino A, Heimer de la Cotera, E. Calcium-dependent smooth muscle excitatory effect elicited by the venom of the hydrocoral Millepora complanata. Toxicon 40: 777-785, 2002. Maillo M, Aguilar MB, Lopez-Vera E, Bulaj G, Craig A, Olivera BM, Heimer de la Cotera E. Conorfamide, a Conus venom peptide belonging to the FMRFamide-like family of neuropeptides. Toxicon 40: 401407, 2002. Torres M, Radwan FFY, Burnett JW, Heimer de la Cotera E, Arellano R. Electrophysiological studies of the venom from the Caribbean jellyfish, Cassiopea xamachana. Toxicon 39: 1297-1307, 2001. Segura Puertas L, Ramos M, Arámburo de la Hoz C, Burnett J, Heimer de la Cotera E. One Linuche mystery solved: all three stages of the coronate scyphomedusae Linuche unguiculata cause seabather’s eruption. Journal of the American Academy of Dermatology 44: 624-628, 2001. Group members: Manuel Aguilar, Ph. D. Assistant Professor Andrés Falcón, B. Sc. Technician 11 REPRODUCTIVE NEUROENDOCRINOLOGY: CELLULAR AND MOLECULAR MECHANISMS INVOLVED IN THE REGULATION OF THE REPRODUCTIVE AXIS Gonzalo Martínez de la Escalera, Ph.D. RELEVANT PUBLICATIONS: Martínez de la Escalera G, Clapp C. Regulation of gonadotropin-releasing hormone secretion: lessons from GT1 immortal GnRH neurons. Archives of Medical Research 32: 486-498, 2001. Beltrán-Parrazal L, Noris G, Clapp C, Martínez de la Escalera G. GABA inhibition of immortalized GnRH neuronal excitability involves GABAA receptors negatively coupled to cyclic AMP formation. Endocrine 14: 189195, 2001. Hernández MM, García Ferreiro RE, García DE, Hernández ME, Clapp C, Martínez de la Escalera G. Potentiation of prolactin secretion following lactotrope escape from dopamine action: I. Dopamine withdrawal augments L-type Ca2+ channels. Neuroendocrinology 70: 20-30, 1999. Martínez de la Escalera G, Choi ALH, Weiner RI. Generation and synchronization of GnRH pulses: intrinsic properties of the GT1-1 GnRH neuronal cell line. Proceedings of the National Academy of Sciences USA 89: 18521855, 1992. Martínez de la Escalera G, Weiner RI. Dissociation of dopamine from its receptor as a signal in the pleiotropic hypothalamic regulation of prolactin secretion. Endocrine Reviews 13: 241-255, 1992. Group members: Michael C. Jeziorski, Ph.D. Research Associate 12 Gabriel Nava, M.Sc. Technician Professor gmel@servidor.unam.mx Ph.D. Physiology, National University of Mexico, Mexico, 1984. Posdoctoral Fellow, University of California, San Francisco, CA., USA, 1985-1988. The laboratory of reproductive neuroendocrinology investigates the molecular and cellular mechanisms by which neural signals are transduced into endocrine messages, with particular focus on the function of the neurons that regulate reproductive function. The elucidation of these basic mechanisms may help explain some dysfunctions of the reproductive axis and have an impact on the control of human fertility and the development of contraception strategies, as well as the improvement of reproductive parameters in farm animals. One focus of present investigations is the gonadotropin-releasing hormone (GnRH) system including: i) the nature of the afferent inputs (catecholamines, aminoacid-derived neurotransmitters such as GABA and neuropeptides) that regulate GnRH neurosecretion, ii) the cellular mechanism(s) responsible for the timing and generation of pulses and iii) the processes involved in the development and establishment of the neuronal architecture and networks. We are also interested in the analysis of cross-talk mechanisms between intracellular signaling pathways that amplify hormone (prolactin and gonadotropins) secretion. Thus, a second theme of study is to analyze the molecular mechanisms involved in the pleiotropic neural regulation of prolactin secretion, with special emphasis on the role of phosphorylation of calcium channels. Our third objective is to understand how various sources of calcium mediate the coupling of stimulus to secretion in gonadotropes. Methods and techniques employed in the laboratory include molecular biology, protein purification and radio-enzymatic quantitation, tissue culture and fluorescence imaging. MOLECULAR CLONING AND MANIPULATION OF IONIC CHANNELS AND NEURORECEPTORS Ataúlfo Martínez-Torres, Ph.D. Assistant Professor ataulfo@inb.unam.mx Ph.D. in Molecular Biology and Genetic Engineering, School of Medicine, UANL, México, 1999. Postoctoral Fellow. University of California, Irvine, CA, USA, 1999-2003. All brain functions depend on the transmission of electrical and chemical signals across myriads of synapses – the sites of contact that link the billions of nerve cells that make up the brain. Essentially, the process of synaptic transmission can be either excitatory or inhibitory, and both are fundamental for all brain functions. In our laboratory we employ a combination of molecular and electrophysiological methods to understand the basis of synaptic transmission. We are currently using voltage clamp, a powerful analytical method to study ion-channels and neurotransmitter receptors expressed in Xenopus oocytes; we combine the results with the information generated by the genome projects of different experimental models such as C. elegans, yeast and even humans. Finally, we are also using gene replacement to revert mutant phenotypes of yeast, especially those in which ion channels are involved. RELEVANT PUBLICATIONS: Fucile S, Palma E, Martinez-Torres A, Miledi R, Eusebi F. The single-channel properties of human acetylcholine alpha 7 receptors are altered by fusing alpha 7 to the green fluorescent protein. Proceedings of the National Academy of Sciences USA 99: 3956-6, 2002. Miledi R, Eusebi F, Martinez-Torres A, Palma E, Tertel F. Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes. Proceedings of the National Academy of Sciences USA 99: 13238-13242, 2002. Martinez-Torres A, Miledi R. Expression of gamma-aminobutyric acid rho 1 and rho 1 Delta 450 as gene fusions with the green fluorescent protein. Proceedings of the National Academy of Sciences USA 98: 19471951, 2001. Martinez-Torres A, Demuro A, Miledi R. GABAρ 1/GABAα1 receptor expression to study receptor desensitization. Proceedings of the National Academy of Sciences USA 97: 3562-3566, 2000. Martinez-Torres A, Vázquez AE, Panicker MM, Miledi R. Cloning and functional expression of alternative spliced variants of the rho1 gamma-aminobutyrate receptor. Proceedings of the National Academy of Sciences USA 95: 4019-4022, 1998. Group members: Carmen Mejía, Ph.D. Research Associate Irma Martínez, M.Sc. Technician 13 NEUROENDOCRINE PHYSIOLOGY Flavio Mena, Ph.D. RELEVANT PUBLICATIONS: Emeritus Professor fmena@servidor.unam.mx Ph.D. in Physiology, National University of Mexico, Mexico, 1975. Diaz N, Huerta I, Marina N, Navarro N, Mena F. Regional mechanisms within anterior pituitary of lactating rats may regulate prolactin secretion. Endocrine 18: 41-46, 2002. Marina N, Morales T, Mena F. Suckling-induced activation of neural c-fos expression at lower thoracic rat spinal cord segments. Brain Research 954: 100-114, 2002. Morales T, Shapiro E, Mena F. Sympathetic innervation of the mammary glands modulates suckling-induced reflex inhibition of milk ejection in rats. Physiology and Behavior 74: 37-43, 2001. Morales T, Shapiro E, Mena F. Beta-adrenergic mechanisms modulate central nervous system effects of prolactin on milk ejection. Physiology and Behavior 74: 119-126, 2001. Aceves C, Rojas-H R, Marina N, Morales MT, Mena, F. Mammary gland sympathetic innervation is a major component on type I deiodinase regulation. Endocrine 11: 115121, 1999. Group members: Tatiana Fiordelisio, Ph. D. Posdoctoral Fellow Nilda A. Navarro, M. Sc. Technician 14 Alejandra Castilla D.V.M. Technician Two lines of research are pursued in this laboratory, involving 1) the regulation of prolactin (PRL) secretion by the rat anterior pituitary (AP) under different physiological conditions and 2) the autonomic regulatory and control mechanisms of the motor apparatus of the mammary gland during milk ejection. With respect to AP PRL, it is known that systemic, hypothalamic, autocrine and paracrine mechanisms regulate its secretion. In the last few years, AP regional factors have been shown to regulate PRL secretion depending upon the physiological condition of the animal. With respect to the second line of research, it was shown that suckling-induced sympathetic neural influences regulate milk ejection, as well as deiodidination of T4 to T3 within the mammary gland. The neural elements involved at the spinal cord level have been identified by histochemical techniques. Finally, it was shown that phasic suckling-induced autonomic arousal was, in turn, regulated by activation of ductal mechanoreceptors and that both PRL and oxytocin may also participate in spinal regulatory mechanisms of the mammary gland. Future research will be oriented to determine the mechanisms involved in regional regulation of AP PRL secretion and to identify the nature of the factors involved. Also, the location and function of ductal mechanoreceptors within the mammary gland will be analyzed, and the involvement of PRL and oxytocin at the spinal level during lactation will be further documented. MOLECULAR STRUCTURE AND FUNCTION OF NEURORECEPTORS AND IONIC CHANNELS IN THE BRAIN Ricardo Miledi, Ph.D. Extraordinary Professor rmiledi@uci.edu Doctorate Honoris Causa by: Universidad del País Vasco, Spain (1992); Universita di Trieste, Italy,2000; Universidad Autonoma de Chihuahua, Mexico, 2000; Universidad Autonoma de Queretaro, Mexico, 2003. Dr. Miledi´s laboratory studies the molecular biology and structure of neuroreceptors, as well as biophysical and pharmacological aspects of proteins participating in brain synaptic transmission. They have characterized a new type of gabaergic receptor (GABAc) in the retina; its molecular, pharmacological, and physiological properties set it apart from classic gabaergic receptors. This group is studying the receptor activity at the level of a single channel, as well as its modulation by second messengers, binding sites for various pharmacological agents, modulating cations, and differential expression in the retina. Another research line is the characterization of receptors for neurotransmitters and ionic channels in glial cells and gliomas. Astrocytes modulate neural electric impulses and the ionic balance of extracellular fluids, whereas oligodendrocytes produce myelin, a substance conferring faster nervous conduction. Recently, it was shown that astrocytes express a wide variety of receptors for neurotransmitters, voltage-dependent ionic channels, and other membrane proteins that were believed to be absent in neurons. This group also studies the molecular basis of the blocking effect of serotonin and serotonergic agents on cholinergic receptors, in particular nicotinic, not only in the neuromuscular junction, but also in neuronal and muscular nicotinic channels expressed in oocytes. These compounds block channels through a voltage dependent mechanism. Since serotonergic agents with therapeutic purposes are widely used, one must bear in mind the possible consequences a serotonergic blockade may convey. They are studying the structure of these molecules to design novel compounds active on diverse neuronal receptors; such compounds have therapeutic potential, mainly in the treatment of affective disorders. RELEVANT PUBLICATIONS: Miledi R, Eusebi F, Martinez-Torres A, Palma E, Tertel F. Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes. Proceedings of the National Academy of Sciences USA 99: 13238-13242, 2002. García-Colunga J, González-Herrera M, Miledi R. Modulation of nicotinic acetylcholine receptors by zinc. Neuroreport 12: 147-150, 2001. Martinez-Torres A, Miledi R. Expression of gamma-aminobutyric acid rho 1 and rho 1 Delta 450 as gene fusions with the green fluorescent protein. Proceedings of the National Academy of Sciences USA 98: 1947-51, 2001. Martinez-Torres A, Demuro A, Miledi R. GABAρ 1/GABAα1 receptor expression to study receptor desensitization. Proceedings of the National Academy of Sciences USA 97: 3562-3566, 2000. García-Colunga J, Awad JN, Miledi R. Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (prozac). Proceedings of the National Academy of Sciences USA 94: 2041-2044, 1997. Group members: Lenin Ochoa de la Paz, Ph.D. Posdoctoral Fellow 15 FUNCTIONAL NEUROANATOMY OF THE HYPOTHALAMUS: NEUROENDOCRINE AND AUTONOMIC REGULATION OF THE STRESS RESPONSE AND REPRODUCTIVE CYCLE Teresa Morales, Ph.D. RELEVANT PUBLICATIONS: Morales T, Sawchenko PE. Brainstem prolactin-releasing peptide neurons are sensitive to stress and lactation. Neuroscience 121: 771-778, 2003. Marina N, Morales T, Mena F. Suckling-induced activation of neural c-fos expression at lower thoracic rat spinal cord segments. Brain Research 954: 100-114, 2002. Morales T, Shapiro E, Mena F. Sympathetic innervation of the mammary glands modulates suckling-induced reflex inhibition of milk ejection in rats. Physiology and Behavior 74: 37-43, 2001. Morales T, Shapiro E, Mena F. Beta-adrenergic mechanisms modulate central nervous system effects of prolactin on milk ejection. Physiology and Behavior 74: 119-126, 2001. Morales T, Hinuma S, Sawchenko PE. Prolactin-releasing peptide is expressed in afferents to the endocrine hypothalamus, but not in neurosecretory neurons. Journal of Neuroendocrinology 12: 131-140, 2000 (cover photography) . Group members: 16 Eugenia Ramos, B.Sc. Technician Assistant Professor marter@servidor.unam.mx Ph.D. in Physiology, Universidad Nacional Autónoma de México, México, 1990. Posdoctoral Fellow, Salk Institute for Biological Studies, La Jolla, CA, USA. 1997-1999. The anatomic and functional organization of brain circuits enables mammals to respond in an integrated and adaptive manner to challenges from internal and external environments. Our research goal is to understand how the brain is organized to control such bodily functions as eating, response to stress and to special neuroendocrine phases such as pregnancy and lactation. The hypothalamus contains cell groups that mediate adaptive responses by multiple neuroendocrine, autonomic and behavioral mechanisms, and these cell groups provide a tractable and functionally important model system. In particular, our work is focused on the brain areas involved in neuroendocrine and autonomic functions. We seek to identify specific molecules that affect communication between cells in these areas, such as hypothalamic peptides, and to learn how synthesis and secretion of these molecules are regulated under stressful or reproductive conditions, as estrous cycle and lactation. We use immediate early genes and other transcription factors as inducible indices of functional activation in order to identify and characterize hypothalamic cell types that are responsive to specific stimulation and afferents that may mediate one or more components of the hypothalamic response. EVOLUTIONARY PHYSIOLOGY OF HALOMETABOLITES AND DEHALOGENASES Carlos Valverde-R, M.D. Professor cavaro@servidor.unam.mx RELEVANT PUBLICATIONS: Posdoctoral Fellow, University of Connecticut, Conn, USA, 1970-1972. The synthesis and catabolism of iodinated compounds are omnipresent processes in the biosphere. This ubiquity indicates the conservation of ancient metabolic pathways, which, in vertebrates, have converged to form the so-called thyroidal systems. Hence, in spite of being the least abundant halogen, iodine is a trace element essential for the synthesis of iodotyrosines and iodothyronines or thyroid hormones (TH). Our general hypothesis is that the selection of two complementary enzymatic mechanisms, halogenation and dehalogenation, has contributed to preserve and diversify the functional role of iodometabolites. Our laboratory focuses on comparative studies of the functional, biochemical and molecular aspects of two types of dehalogenases: 1) thyroid dehalogenase (tDh), which catalyses intra-thyroidal dehalogenation of mono- and diodo-tyrosine (MIT and DIT, respectively), the iodoaminoacid precursors of TH, and 2) iodothyronine-deiodinases (IDs), which are amply distributed in organisms and include three isotypes (D1, D2 and D3) that catalyze the sequential removal of the iodine atoms from TH. The IDs catalyze the deiodination of iodometabolites, which not only recycles the iodine necessary for TH synthesis, but also controls the bioactivity of TH in an organ-specific manner. Our recent findings in this field can be summarized as follows: the molecular, biochemical and functional characterization of D1 and D2 from a sea-water teleost; the biochemical and functional characterization of hepatic D1 from a reptile; the biochemical characterization of a tDh enzyme which is operationally distinct from ID activity in the rat thyroid gland. Orozco A, Villalobos P, Jeziorski MC, Valverde-R C. The liver of Fundulus heteroclitus expresses deiodinase type 1 mRNA. General and Comparative Endocrinology 130: 8491, 2003. Orozco A, Villalobos P, Valverde-R C. Environmental salinity selectively modifies the outer-ring deiodinating activity of liver and kidney in the rainbow trout. Comparative Biochemistry and Physiology, Part A. 131: 387-395, 2002. Orozco A, Jeziorski MC, Linser PJ, Greenberg RM, Valverde-R C. Cloning of the gene and complete cDNA encoding a type 2 deiodinase in Fundulus heteroclitus. General and Comparative Endocrinology 128: 162-167, 2002. Orozco A, Linser PJ, Valverde-R C. Kinetic characterization of outer-ring deiodinase activity (ORD) in the liver, gill and retina of Fundulus heteroclitus. Comparative Biochemistry and Physiology, Part B 126: 283-290, 2000. Fenton B, Valverde-R C. Hepatic outer-ring deiodinase in a Mexican endemic lizard (Sceloporus grammicus). General and Comparative Endocrinology 117: 77-88, 2000. Group members: Aurea Orozco, Ph. D. Assistant Professor Lucia Nikolaia López, Ph. D. Posdoctoral Fellow Patricia Villalobos, M. Sc. Technician 17 In this department diverse aspects of the development of the nervous system of invertebrates and vertebrates are studied using molecular, morphological, electrophysiological, and behavioral methods. Signal transduction mechanisms during the development of the fruit fly, control of neural differentiation during the embryonic stage, and sexual dimorphism in the brain of vertebrates are among the issues investigated, as well as the effect of various environmental agents such as malnutrition, drugs, and hormones capable of having remarkable impacts on the structure and function of the nervous system. Processes regulating sleep, different strategies of neurological rehabilitation, and neurophysiological mechanisms of pain and experimental epilepsy are other matters addressed in this department. PRINCIPAL INVESTIGATORS Alfonso Cárabez-Trejo León Cintra Miguel Condés-Lara Sofía Díaz Jorge Larriva-Sahd Juan Riesgo-Escovar Manuel Salas Alfredo Varela-Echavarría 20 STRUCTURAL, CELLULAR, AND MOLECULAR ASPECTS OF NEUROTOXICITY IN THE CNS CAUSED BY INHALATION OF INDUSTRIAL SOLVENTS (THINNER-TYPE) USED FOR PAINTING Alfonso Cárabez-Trejo, Ph.D. Professor carabez@servidor.unam.mx Ph,D. in Biochemistry, National University of Mexico, Mexico, (1986) Posdoctoral Fellow, Johns Hopkins University, USA, (1971-1972), Cornell University, USA, (1974) Paint-thinner is perhaps the inhalant most widely used by youths and children as a stimulant of the central nervous system. Its widespread use is due in part to its organoleptic properties, desired effects (hallucinations), low price and convenient packaging. The low price of paint thinner makes it very popular with consumers who have minimal economic resources. The morphological and functional damage induced by short or long term inhalation, either wittingly or involuntarily (inadequate working conditions), depends on the duration and quantity of use (or abuse). Long term pathologic alterations are irreversible. Solvent (paint-thinner) sniffing induces mental retardation and general failure in brain, hepatic, pulmonary, renal etc. functions. This generalized dysfunction finally leads to drug addiction and ultimately to the death of the individual. Previous studies focused in general on the social, pharmacological, neurofunctional and psychological disorders were performed with involuntary sniffers or with voluntary sniffers imprisoned in Juvenile Rehabilitation Centers. With the purpose of understanding the brain damage of those individuals who voluntarily sniff industrial solvents (paint thinner), we developed a murine model primarily to study brain damage. We applied several laboratory techniques of molecular and cellular biology such as: electron microscopy, spectrophotometry, gel electrophoresis. Our results indicate that the Brain Blood Barrier (BBB) is the function most affected. The BBB results from the intimate association between the glial astrocytes and the endothelial cells from the cerebral microvasculature. We have found that after solvent inhalation the endothelial cell tight junctions are broken, due in part to damage to the end feet of the astrocytes. Astrocytes are the cells responsible for the phenotypic expression of the endothelial tight junctions that form the basis of the BBB. RELEVANT PUBLICATIONS: Carrillo-López A, Cruz-Hernández A, Cárabez-Trejo A, Guevara-Lara F, Paredes-López O. Hydrolytic activity and ultrastructural changes in fruit skins from two prickly pear (Opuntia sp.) varieties during storage. Journal of Agricultural and Food Chemistry 50: 1681-1685, 2002. Domínguez-Ramirez L, Mendoza-Hernández G, Cárabez-Trejo A, Gómez-Puyou A, Tuena de Gómez-Puyou M. Equilibrium between monomeric and dimeric mitochondrial F!-inhibitor protein complexes. FEBS Letters 253: 731-734, 2001. Francisco T, Carvajal K, Cruz D, Cárabez A, Chávez E. Effect of perezone on arrhytmias and markers of cell injury during reperfusion in the anesthetized rat. Life Sciences. 65: 1615-1623, 1999. Cárabez-Trejo A, Sandoval F, Palma-T L. Ultrastructural changes of tissues produced by inhalation of thinner in rats. Microscopy Research and Technique 40: 56-62, 1998. Gómez-Lojero C, Pérez Gómez B, PradoFlores G, Krogmann DW, Cárabez A, Peña-Díaz A. Phycobilisomes of the Cyanobacterium Arthrospira (Spirulina) maxima. International Journal of Biochemistry and Cell Biology 29:1191-1205, 1997. Group members: Francisca Sandoval, B.Sc. Technician 21 IMPACT OF MALNUTRITION ON THE DEVELOPING CENTRAL NERVOUS SYSTEM AND CIRCADIAN SYSTEM ORGANIZATION IN THE RAT León Cintra, Ph.D. RELEVANT PUBLICATIONS: Cintra L, Durán P, Guevara MA, Aguilar A, Castañon-Cervantes O. Pre- and post-natal protein malnutrition alters the effect of rapid eye movements sleep-deprivation by the platform-technique upon the electrocorticogram of the circadian sleep-wake cycle and its frequency bands in the rat. Nutritional Neuroscience 5: 91-101, 2002. Durán P, Galván A, Granados L, AguilarRoblero R, Cintra L. Effects of protein malnutrition on the vigilance states and their circadian rhythms in 30-day-old rats submitted total sleep deprivation. Nutritional Neuroscience 2: 127-138, 1999. Aguilar-Roblero R, Salazar-Juárez A, RojasCastañeda J, Escobar C, Cintra L. Organization of circadian rhythmicity and suprachiasmatic nuclei in malnourished rats. American Journal of Physiology 273 (Reg Int Comp Physiol 42): R1321-R1331, 1997. Cintra L, Aguilar A, Granados L, Galván A, Kemper T, DeBassio W, Galler J, Morgane P, Durán P, Díaz-Cintra S. Effects of prenatal protein malnutrition on hippocampal CA1 pyramidal cells in rats of four age groups. Hippocampus 7: 192-203, 1997. Morgane PJ, Austin-LaFrance R, Bronzino J, Tonkiss J, Díaz-Cintra S, Cintra L, Kemper T, Galler JR. Prenatal malnutrition and development of the brain. Neuroscience and Biobehavioral Reviews 17: 91-128, 1993. Group members: 22 Pilar Durán Hernández, Ph.D. Research Associate Professor cintra@servidor.unam.mx Ph. D. in Sciences (Biology), National University of Mexico, Mexico, 1985. Postdoctoral Fellow, Worcester Foundation for Experimental Biology. Shrewsbury, Mass., USA. 1978-1981. We are interested in the development of the Central Nervous System and the impact of protein malnutrition on it. In mammals, this kind of malnutrition alters several homeostatic and circadian functions that exhibit neural plasticity such as the sleep-wake cycle, locomotor activity, water intake and brain temperature as well as some cognitive and behavioral processes. Prenatal or chronic malnutrition affects the sleep recovery mechanism after total or selective sleep deprivation, altering its quantitative, qualitative and circadian characteristics. Using spectral analysis of brain electrical activity, malnutrition was found to alter those frequencies implicated in the theta rhythm generated into the hippocampal formation (HF). HF is associated with REM sleep generation and with learning and memory processes. These results, and the effects on the functional relationships in the brains of juvenile rats suggest that the associated cognitive and behavioral functions could be altered. Our group has also demonstrated that several circadian rhythms (locomotor activity, temperature and water intake) are out-of-phase or affected by malnutrition, implying alterations in the suprachiasmatic nuclei, which were confirmed by histology. Projects in progress: “Stress as an altered response by nutritional state” “Cortical and Hippocampal functional relationships in the malnourished rat PAIN AND EPILEPSY Miguel Condés-Lara, Ph.D. Associate Professor condes@servidor.unam.mx Ph.D. in Sciences (Neurosciences). Université Pierre y Marie Curie, Paris, 1983. Posdoctoral Fellow, National Center for Scientific Research (CNRS), Université Pierre y Marie Curie Paris, France, 1982-1983. The main lines of research concern the mechanisms of pain and analgesia and experimental epilepsy. In both lines, we study the neuronal interactions, biochemical mechanisms, neuro-anatomical relationships and how they correlate with behavior. Electrophysiological, pharmacological, histological, behavioral, computational and image analysis strategies are used to establish the possible correlations between different central nervous system structures and their functions under normal conditions and during different pain states, analgesia as well as during the development and propagation of experimental epilepsy activities. The study of pain and analgesia attempts to document an ascendant neuronal mechanism implicated in pain suppression. This entails the study of neuronal pathways related to pain and analgesia, especially mesencephalic, thalamic, and cortical interactions as well as those taking place at the spinal cord level. In experimental epilepsy we are interested in the neuro-anatomical mechanisms participating in the generation, propagation and generalization of epileptic activity. Currently we work on the mechanisms related to the propagation of epileptic activity and to axonal transport. The laboratory projects have research and academic collaboration with laboratories in Mexico City, Strasbourg, France and London, England. Also, interdisciplinary projects are developed to support other lines of investigation. In particular, we have a project describing the electrophysiological characteristics of interfascicular neurons, whose functions we seek to establish. In summary, we study the relationships between structures of the nervous system and their functions: from synaptic interaction to behavior. This laboratory has an integrative approach. RELEVANT PUBLICATIONS: Condés-Lara M, Marina-González N, Martínez-Lorenzana G, Luis Delgado O, FreundMercier MJ. Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities. Brain Research 976: 75-81, 2003. Condés-Lara M, Martinez-Cabrera G, Martinez-Lorenzana G, Larriva Sahd J. Electrophysiological evidence that the interfascicular cells of the rat anterior commissure are neurons. Neuroscience Letters 323: 121-124, 2002. Condés-Lara M, Talavera-Cuevas E, Larriva-Sahd J, Martínez-Lorenzana G. Different wheat germ agglutinin-horseradish peroxidase labeling in structures related to the development of amygdaline kindling in the rat. Neuroscience Letters 299: 13-16, 2001. Martínez-Lorenzana G, Talavera-Cuevas E, Sánchez-Alvarez M, Condés-Lara M. Effects of kindling in WGA-HRP labeling in neurons of the interamygdaloid pathway. Neuroscience Letters 281: 135-138, 2000. Condés-Lara M, Omaña Zapata I, León Olea M, Sánchez Alvarez, M. Dorsal raphe and nociceptive stimulations evoke convergent responses on the thalamic centralis lateralis and medial prefrontal cortex neurons. Brain Research 499: 145-152, 1989. Group members: Gerardo Rojas-Piloni, Ph.D. Posdoctoral Fellow Guadalupe Martínez, Ph.D. Technician 23 PLASTICITY IN THE MALNOURISHED AND AGEING HIPPOCAMPUS: ANATOMY AND BEHAVIOURAL STUDIES Sofía Díaz, Ph.D. RELEVANT PUBLICATIONS: Díaz-Cintra S, Yong A, Aguilar VA., Xiaoning Bi, Lynch G, Ribak CH. Ultraestructural analysis of changes in neuronal features of hippocampal pyramidal cells treated with cathepsins inhibitor from Apoliprotein Edeficient mice. Journal of Neurocytology 33: 37-48, 2004. Cerutti SM, Díaz-Cintra S, Cintra L, Ferrari EA. Operant discriminative learning and evidence of subtelencephalic plastic changes after long-term detelencephalation in pigeons. Neural Plasticity 10: 247-66, 2003. Quiroz C, Martinez I, Quirarte GL, Morales T, Díaz-Cintra S, Prado-Alcalá R. Enhanced inhibitory avoidance learning prevents the memory-impairing effects of posttraining hippocampal inactivation. Experimental Brain Research 153: 400-402, 2003. Granados-Rojas L, Larriva-Sahd J, Cintra L, Gutiérrez-Ospina G, Rondán A, Aguilar A, Díaz-Cintra S. Prenatal protein malnutrition decreases hippocampal CA3 asymmetric synaptic contacts in adult rats. Brain Research 933: 91-173, 2002. Martínez I, Quirarte G, Díaz-Cintra S, Quiróz C, Prado-Alcalá R. Effects of lesions of hippocampal fields CA1 and CA3 on acquisition of inhibitory avoidance. Biological Pshychology/ Pharmacopsychology 46: 97-103, 2002. Group members: 24 Azucena Aguilar, M.Sc. Technician Associate Professor yoldi@servidor.unam.mx Ph.D. in Sciences. National University of Mexico, Mexico, 1988. Postdoctoral Fellow, Boston City Hospital, Massachusetts, USA. 1979-1980. . Malnutrition during pre and postnatal development of the nervous system produces cognitive impairments in adult life. One of the anatomical structures associated with these functions is the hippocampus, whose plasticity is well preserved during cellular growth, differentiation, maturation and ageing. In order to determine if malnutrition affects this structure, we have established models of malnutrition during rat brain development. Using these models, we reported reductions in certain cellular parameters as well as the volume of the mossy fibers, density of the spines and synaptic contacts. These anatomical changes were also correlated with decrease in a spatial learning task such as the water maze test. Recently we designed similar studies in 22-month-old rats in order to probe if the hippocampal plasticity still persists in pre and postnatal malnourished animals. In collaboration with the University of California, we have developed a similar, but in vitro model of ageing by increasing the number of lysosomal bodies. The aim is to detect early cellular changes with emphasis on their de-connexion process which is one of factors that produces the memory alterations in Alzheimer’s disease (AD). In addition, we will determine if malnutrition accelerates this process, particularly in pyramidal cells of the hippocampus. Thus, the research lines in our laboratory for both the malnourished and ageing hippocampus include: 1) cellular and ultrastructural studies; 2) behavioral changes; 3) the possibility to reverse these alterations and 4) cellular mechanisms related with the pathology AD. A) GONADAL SEX HORMONES AND SEXUALLY DIMORPHIC PHENOTYPE B) CYTOLOGICAL ORGANIZATION OF THE LIMBIC SYSTEM Jorge Larriva-Sahd, Ph.D. Associate Professor jlsneuro@servidor.unam.mx Ph.D. in Anatomy, UCLA, Los Angeles, CA., USA, 1987. Postdoctoral Fellow. Brain Research Institute. UCLA, Los Angeles, CA, USA, 1983. Since 1987, we have been studying the phenomena of structural and, more recently, molecular induction by gonadal sex hormones. In the former, we have shown that the medial preoptic and ventral-medial nuclei exhibit a sexually dimorphic synaptic density, being larger in the male. We have also provided evidence that these phenotypic differences are dramatically influenced by endogenous testosterone, as neonatal gonadectomy of the male rat reduces the synaptic density of these nuclei to that recorded in the normal female. More recently, we have demonstrated that testosterone induces hypertrophy of the rat´s anterior commissure (AC), irrespective of the animal’s sex. Investigating this, we became interested in an intriguing group of neurons that lie confined among the axonal fascicles of the rat, mouse, gerbil, hamster, monkey and human AC, the so-called interfascicular neurons (IFNs). Furthermore, these neurons include short axon (interneurons) and projection types. Based on these observations, it was proposed that the white matter (i.e. AC) may be a site of integration of nerve impulses delivered by commissural collaterals. Although the possible site(s) of projection remains to be found, we have been able to document IFNs inputs; in fact, the periamygdaloid and infralimbic (medial frontal) cortices, as well as the anterior olfactory nucleus send direct projections to IFNs, as documented by electrophysiology. We are currently investigating: 1) the connectivity (i.e. outputs) of IFNs, 2) the structure of the bed nuclei of the stria terminalis in normal and stressed rats, and 3) the sexually dimorphic genomic expression as a function of ontogenic development and sex hormone environment. RELEVANT PUBLICATIONS: Larriva-Sahd J. Juxtacapsular nucleus of the stria terminalis of the adult rat: extrinsic inputs, cell types, and neuronal modules: a combined Golgi and electron microscopic study. Journal of Comparative Neurology 475: 220-237, 2004. Condés-Lara M, Martínez G, MartínezLorenzana G, Larriva-Sahd J. Electrophysiological characteristics of interfascicular neurons of the rat anterior commissure. Neuroscience Letters 121: 121-124, 2002. Larriva-Sahd J, Condés-Lara M, MartínezCabrera G, Varela-Echavarría A. Histological and ultrastructural characterization of Interfascicular neurons in the rat anterior commissure. Brain Research 931: 81-91, 2002. Larriva-Sahd J, Orozco-Estévez H, CondésLara M. Perinatal administration of testosterone induces hypertrophy of the anterior commissure in adult male and female rats. Neuroscience Letters 241: 119-122, 1998. Larriva-Sahd J, Rondán-Zárate A, RamírezDegollado M. Sexually dimorphic contribution from the fornix to the ventromedial hypothalamic nucleus: A quantitative electron microscopic study. Neuroscience Letters 200: 147-150, 1995. Group members: Gema Martínez, B.Sc. Technician 25 CELLULAR SIGNALING IN PLURICELLULAR EUKARYOTES DURING DEVELOPMENT AND SENSORY TRANSDUCTION Juan Riesgo-Escovar, Ph.D. RELEVANT PUBLICATIONS: Vazquez O, Cañedo-Merino R, Diaz-Muñoz M, Riesgo-Escovar JR. Biochemical characterization, distribution and phylogenetic analysis of Drosophila melanogaster ryanodine and IP3 receptors, and thapsigargin-sensitive Ca2+ ATPase. Journal of Cell Science 116: 2483-2494, 2003. Boehni R, Riesgo-Escovar JR, Oldham S, Brogiolo W, Stocker H, Andruss B, Beckingham K, Hafen E. Autonomous control of cell and organ size by CHICO, a Drosophila homologue of vertebrate Insulin Receptor Substrates, IRS1-4. Cell 97: 865-875, 1999. Riesgo-Escovar JR, Hafen E. Common and distinct roles of dFos and dJun during Drosophila development. Science 278: 669672, 1997. Riesgo-Escovar JR, Hafen E. Drosophila jun kinase regulates expression of dpp via the etsdomain protein aop and the AP-1 transcription factor dJun during dorsal closure. Genes and Development 11: 1717-1727, 1997. Riesgo-Escovar JR, Raha D, Carlson J. Requirement for a phospholipase C in odor response: Overlap between olfaction and vision in Drosophila. Proceedings of the National Academy of Sciences USA 92: 2864-2868, 1995. Group members: 26 Teresa Peña, Ph.D. Technician Assistant Professor riesgo@inb.unam.mx Ph.D. (Biology), Yale University, New Haven, CT., USA. 1995. Posdoctoral Fellow. Zoologisches Institut, Zürich University, Switzerland. 1995-1997. Our laboratory studies signal transduction pathways during development, particularly the Jun kinase signaling pathway. The Jun kinase pathway is required during development and wound healing for cell shape change, and also to mediate cellular responses to stress. These signaling pathways are highly conserved throughout evolution, and many of their constituent genes are also involved in the onset and progression of cancer and metastasis. We use Drosophila melanogaster, the common fruit fly, to study these pathways since we can employ different methodologies (molecular, cellular, biochemical, electrophysiological, behavioral and genetic experiments), in a multidisciplinary approach. Our method starts with the isolation of new mutants in these pathways, and continues with their detailed characterization using the aforementioned methods and techniques. We employ the same approach to study sensory transduction, particularly vision and olfaction. Sensory transduction pathways are also highly evolutionarily conserved. Our goal is a better understanding of the communication systems that the cells use during development and the pathways they employ to receive and convey sensory information. EFFECTS OF PERINATAL FOOD RESTRICTION ON NEUROPHYSIOLOGICAL DEVELOPMENT OF THE RAT Manuel Salas, Ph.D. Professor masal@servidor.unam.mx Ph.D. in Biomedical Sciences, National University of Mexico, Mexico, 1996. Postdoctoral Fellow, University of California, Los Angeles, CA, USA. 1968-1970. Our current research investigates the effects of epigenetic factors upon morphological, electrophysiological and behavioral development in the rat. Our major interests are to understand the possible mechanisms underlying the alterations in morphological and sensorial development, the abnormalities in the capacity of brain tissue to generate both spontaneous and evoked potentials to sensory cues, and long-term behavioral alterations associated with neonatal food and sensory restrictions. We are developing different routines of early sensory stimulation in order to ameliorate both morphological and behavioral development. In addition, we analyze altered mechanisms of mother-litter interactions resulting from perinatal food and sensory deprivation in the laboratory rat. RELEVANT PUBLICATIONS: Pérez-Torrero E, Torrero C, Salas M. Effects of perinatal undernourishment on neuronal development of facial motor nucleus in the rat. Brain Research 905: 54-62, 2001. Salas M, Regalado M, Torrero C. Recovery of long-term maternal deficiencies of neonatally underfed rats by early sensory stimulation: effects of successive parturitions. Nutritional Neuroscience 4: 311-322, 2001. Torrero C, Pérez E., Regalado M, Salas M. Pattern of sucking movements during artificial feeding of neonatally undernourished rats. Nutritional Neuroscience 3: 245-254, 2000. Salas M, Torrero C, Pulido S. Long-term alterations in the maternal behavior of neonatally undernourished rats. Physiology and Behavior 33: 273-278, 1984. Salas M, Díaz S, Nieto A. Effects of neonatal food deprivation on cortical spines and dendritic development of the rat. Brain Research 73: 139-144, 1974. Group members: Esther Pérez, Ph.D. Research Associate Carmen Torrero, B.Sc. Technician Mirelta Regalado, M.Sc. Technician 27 A) CONTROL OF LONGITUDINAL AXON GUIDANCE IN THE DEVELOPING BRAIN B) MOLECULAR CONTROL OF RETICULOSPINAL NEURON DIFFERENTIATION Alfredo Varela-Echavarría, Ph.D. RELEVANT PUBLICATIONS: Montiel HL, Meléndez-Herrera E, CepedaNieto AC, Mejía-Viggiano C, Larriva-Sahd J, Guthrie S, Varela-Echavarría A. Diffusible signals and fasciculated growth in reticulospinal axon pathfinding in the hindbrain. Developmental Biology 255: 99-112, 2003. Larriva-Sahd J, Condés-Lara M, Martínez-Cabrera G, Varela-Echavarría A. Histological and ultrastructural characterization of interfascicular neurons in the rat anterior commissure. Brain Research 931: 81-89, 2001. Varela-Echavarría A, Guthrie S. Molecules making waves in axon guidance (review). Genes and Development 11: 545-557, 1997. Varela-Echavarría A, Tucker A, Püschel A, Guthrie S. Motor axon subpopulations respond differentially to the chemorepellants netrin-1 and semaphorin D. Neuron 18: 193-207, 1997. Varela-Echavarría A, Pfaff SL, Guthrie S. Differential expression of LIM homeobox genes among motor neuron subpopulations in the developing brain stem. Molecular and Cellular Neuroscience 8: 242-257, 1996. Group members: Elisa Tamariz Domínguez, Ph.D. Research Associate 28 Carmen Mejía, M.Sc. Technician Assistant Professor varela@inb.unam.mx Ph.D. in Molecular Genetics and Microbiology, University of Medicine and Dentistry, NJ, USA. 1994. Posdoctoral Fellow, University of London, UK, 1994-1998. The central aim of the work in our laboratory is to identify and characterize the mechanisms that guide axons along longitudinal routes in the developing vertebrate brain. With these studies we will elucidate the main processes that control the establishment of the major axonal tracts that are used as the substrate to develop the highly complex connectivity patterns that characterize the adult brain. Our studies have implicated several homeodomain transcription factors in reticulospinal differentiation and suggest that discrete transversal domains in the developing brain act as axon growth organizers attracting or repelling several types of longitudinal axons. The main projects underway are: a) Molecular mechanisms that control axonal projection of reticulospinal neurons. b) Molecular control of reticulospinal neuron differentiation. c) Molecular control of nigrostriatal axon pathfinding. d) Molecular control of axonal growth of the tract of the post-optic commissure. e) Modulation of the response to semaphorins by cranial motor neurons. The research carried out in this department analyzes the neurobiological mechanisms participating in the control of behavior and in complex cerebral processes pertaining to animals and humans. The diverse aspects investigated relate to the expression of sexual behavior and neurochemical, cellular, and physiological phenomena underlying memory and learning processes, as well as different models of neurodegenerative diseases. By means of electrophysiological and neuroimaging methods, the foundations within the brain of mental activity such as language, emotions, and conscience are studied, as well as neurophysiological mechanisms of time perception in primates. New diagnostic methods of early brain damage are also being addressed, as well as neurohabilitation techniques and generation of new methods of functional analysis of neuroimages obtained by magnetic resonance. PRINCIPAL INVESTIGATORS Fernando Barrios Antonio Fernández-Bouzas Thalía Fernández Magda Giordano Thalía Harmony Hugo Merchant Isabel Miranda Raúl Paredes Roberto Prado-Alcalá Gina Quirarte Víctor Ramírez-Amaya 30 FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE HUMAN CENTRAL NERVOUS SYSTEM AND DIGITAL IMAGE ANALYSIS SYSTEMS Fernando Barrios, Ph.D. Associate Professor barrios@slytherin.inb.unam.mx Ph.D. in Physics, University of Cincinnati, OH. 1991. Fogarty Postdoctoral Fellow, NIMH-CBDB in Dr. Daniel Weinberger’s Branch, 1991-1992. I study the different applications of functional magnetic resonance imaging of the central nervous system and the different processes of image analysis that can be used to improve and correct for motion and signal instabilities. My research group is currently using functional magnetic resonance imaging to map fine motor activity in the disorder known as “essential familial tremor”, and to determine the possible consequences or significance of mapping plasticity in the human brain. We have worked also in magnetic resonance proton spectroscopy in children with attention deficit disorder and hyperactivity. Finally, we have studied the viability of mapping motor and sensory activity of the human spinal cord with functional magnetic resonance imaging in order to apply such studies in amputee patients. In my laboratory we have also developed image segmentation software and image analysis software for MRI and confocal microscopy imaging. RELEVANT PUBLICATIONS: Barrios FA, González-Santos L, Favila R, Rojas R, Sánchez-Cortazar J. Adaptive robust Filters in MRI, Proceedings of SPIE, Medical Imaging 2002, Image Processing, Ed. Milan Sonka and Michael J. Fitzpatrick, Volume 4684, pp. 1028-1033, 2002. Barrios FA, Rodríguez AO, Brandan M. (Editors). “Fith Mexican Symposium on Medical Physics”, Juriquilla Querétaro, México, AIP Conference Proceedings Vol. 593, ISBN 07354-0036-9, New York, 2001. Rodríguez AO, Rojas R, Barrios FA. Year 2000 status of MRI in México, Letter to the Editor, Journal of Magnetic Research Imaging 13: 813-817, 2001. Condes-Lara M, Barrios FA, Romero-Romo J, Rojas R, Salgado P, Sánchez-Cortazar J. Brain somatic representation of phantom and intact limb: A fMRI study case report. European Journal of Pain 14: 239-245, 2000. Moonen CTW, Barrios FA, Zigun JR, Gillen J, Liu G, Sobering G, Sexton R, Frank JA, Weinberger DR. Functional brain MR imaging based on bolus tracking with a fast T2* sensitized gradient-echo meted. Journal of Magnetic Research Imaging 12: 379-385, 1994. Group members: Leopoldo González, M.Sc. Technician 31 BRAIN VOLUMES AND MEMORY TASKS Antonio Fernández-Bouzas, Ph.D. RELEVANT PUBLICATIONS: Associate Professor fabouzas@servidor.unam.mx Ph.D. Neurobiology, National University of Mexico, Mexico, 1999. Fernández-Bouzas A, Harmony T, Fernández T, Ricardo-Garcell J, Casián G, SánchezConde R. Cerebral blood flow and sources of abnormal EEG activity (VARETA) in neurocysticercosis. Clinical Neurophysiology 112: 2281-2287, 2001. Fernández-Bouzas A, Harmony T, Bosch J, Aubert E, Fernández T, Valdés P, Silva J, Marosi E, Martínez-López M, Casián G. Sources of abnormal EEG activity in the presence of brain lesions. Clinical Electroencephalography 30: 46-52, 1999. Fernández-Bouzas A, Harmony T, Marosi E, Fernández T, Silva J, Rodríguez M, Bernal J, Reyes A, Casián G. Evolution of cerebral edema and its relationship with power in theta band. Electroencephalography and Clinical Neurophysiology 102: 279-285, 1997. Fernández-Bouzas A, Pérez-Montemayor D, Harmony T, Marosi E, Becker J, Rodríguez M, Reyes A, Fernández-Harmony T. EEG and skeletal development in children with different psychosocial characteristics. International Journal of Neuroscience 58: 105-111, 1991. Fernández-Bouzas A, Harmony T, Hernández-Zayas H, Marín Fernández G. Stenosis and occlusion of the common carotid artery by lateral movements of the head. Acta Neurologica Latinoamericana 5: 24-32, 1969. 32 In this project we evaluate the relationships between the volume of different structures such as the frontal lobes, the hippocampus, gyrus rectus, cingulate, putamen, globus pallidus and the performance in different memory tests. All structures are measured manually in the Magnetic Resonance Images of the brains. The total volumes of gray matter and of white matter are measured by a semi-automatic procedure. All subjects have an academic universitary degree, they were professionally active, and have ages between 21 and 76 years old. Our hypothesis is that significant relationships will exist between the volumes of the different structures and the performance on different memory tests, independent of age. Variable Resolution Electromagnetic Tomography (VARETA) and Brain Lesions (infarcts and intracraneal tumors). In this research we project the sources of electromagnetic activity onto the magnetic resonance images of the brain of each subject. This takes into account the brain deformation produced by the tumor. Up to now we have projected the sources onto the computerized brain of the Montreal Institute, with good results. Now we want to have the original image of the patient’s brain, with the deformation produced by the lesion, in order to project onto it the functional information from EEG sources. In this way the image will have both the anatomical and functional information. NEUROFEEDBACK Thalía Fernández, Ph.D. Assistant Professor thalia@servidor.unam.mx Ph,D. in Physiology National University of Mexico, Mexico, 1996. Posdoctoral Fellow of California, San Diego, USA, 1997-1998. Neurofeedback (NFB) is an operant conditioning procedure, by which the subject learns to control his/her electroencephalographic (EEG) activity. NFB treatment is an effective therapy in humans to reduce the behavioral symptoms of children and adults with attention deficit/hyperactivity disorder, depression, obsessive-compulsive disorder, schizophrenia, alcoholism, epilepsy, etc. Our lab has been working for more than 20 years in the behavioral and electroencephalographic characterization of children with learning disorders (LD). There is no efficient therapy for these disorders, and for this reason we have explored other methods such as NFB to treat them. Initially, we demonstrated that NFB (using theta/alpha protocol) applied in the brain region with the most abnormal value of the theta/alpha quotient, was an effective treatment independent of the attention provided to the child by the therapist and/or parents and other placebo effects. The group given NFB showed more positive behavioral changes and more changes toward a normal EEG maturation than the control group; in 80% of children treated with NFB, the abnormal EEG patterns disappeared. Our goal is to optimize the NFB treatment; also we will explore the effects of NFB depending on the source of EEG current, coherence, and gamma band, in order to apply NFB on the basis of these measures. Follow up studies of these subjects will allow us to corroborate the permanence of the effect that is reported in the literature. As a parallel project, we also want to explore the effect that NFB may have upon memory in the elderly, a pioneering study in this field. RELEVANT PUBLICATIONS: Fernández T, Herrera W, Harmony T, DíazComas L, Santiago E, Sánchez L, Bosch J, Fernández-Bouzas A, Otero G, Ricardo-Garcell J, Barraza C, Aubert E, Galán L, Valdés P. EEG and behavioral changes following neurofeedback treatment in learning disabled children. Clinical Electroencephalography 34: 145-152, 2003. Fernández T, Harmony T, Fernández-Bouzas A, Silva J, Herrera W, Santiago-Rodríguez E, Sánchez L. Sources of EEG activity in learning disabled children. Clinical Electroencephalography 33: 160-164, 2002. Fernández T, Harmony T, Silva J, Galán L, Díaz-Comas L, Bosch J, Rodríguez M, Fernández-Bouzas A, Yáñez G, Otero G, Marosi E. Relationship of specific EEG frequencies at specific brain areas with performance. Neuroreport 9: 3681-3687, 1998. Harmony T, Marosi E, Becker J, Rodríguez M, Reyes A, Fernández T, Silva J, Bernal J. Longitudinal quantitative EEG study of children with different performances on a reading-writing test. Electroencephalography and Clinical Neurophysiology 95: 426-433, 1995. Harmony T, Marosi E, Díaz de León AE, Becker J, Fernández Harmony T. Analysis of electroencephalographic maturation. En: E.R. John, T. Harmony, L. Prichep, M. Valdés, P. Valdés (Eds.). Machinery of the mind, Birkhauser, Boston, pp. 360-375, 1990. Group members: Josefina Ricardo Garcell, Ph.D. Technician 33 ANIMAL MODELS OF INJURY AND REPAIR IN THE CENTRAL NERVOUS SYSTEM, A NEUROBEHAVIORAL APPROACH Magda Giordano, Ph.D. RELEVANT PUBLICATIONS: Rodríguez VM, Carrizales L, Mendoza MS, Fajardo OR, Giordano M. Effects of sodium arsenite exposure on development and behavior in the rat. Neurotoxicology and Teratology 24: 743-750, 2002. Mena-Segovia J, Cintra L, Prospéro-García O, Giordano M. Changes in sleep-waking cycle after striatal excitotoxic lesions. Behavioral Brain Research 136: 475-481, 2002. Rodríguez VM, Carrizales L, Jiménez-Capdeville ME, Dufour L, Giordano M. The effects of sodium arsenite exposure on some neurobehavioral parameters in the albine rat. Brain Research Bulletin 55: 301-308, 2001. Giordano, M., Mejía-Viggiano, M.C. Gender differences in spontaneous and MK-801induced activity after striatal lesions. Brain Research Bulletin 56: 553-561, 2001. Giordano M, Takashima H, Poltorak M, Geller HM, Freed WJ. Constitutive expression of glutamic acid decarboxylase (GAD) by striatal cell lines immortalized using the tsA58 allele of the SV40 large T antigen. Cell Transplantation 5:563-575, 1996. Group members: 34 Soledad Mendoza, B. Sc. Technician Associate Professor giordano@servidor.unam.mx Ph.D. in Experimental Psychology, University of Cincinnati, Cincinnati, Ohio, USA, 1991. Postdoctoral Fellow. NIMH-NCSE, USA, 1991-1994. I study injury and repair in the nervous system using a neurobehavioral approach. The behavioral paradigms with which I work, are the excitotoxicity model represented by the kainic acid model of Huntington´s disease, experimental models of epilepsy, and neurotoxicology of heavy metals. With regards to the first model, I study behavioral and cellular changes that take place after intrastriatal administration of excitotoxins. Because of the prominent role of the basal ganglia in motor and cognitive functions, I study locomotor behavior, learning and the waking-sleeping cycle, and evaluate their disruption after striatal lesions. I look for evidence of synaptic reorganization, such as axon outgrowth, expression of trophic factors, or other molecules that may play a role in plastic changes within the lesioned striatum. Our aim is to determine if these cellular changes correlate with behavioral measures. With respect to the second model, I am interested in evaluating if transplants of gamma-amino butyric (GABA) producing cells could reduce or protect against seizures in well-known animal models of epilepsy. Our working hypothesis is that increases in GABA levels within certain specific brain areas will reduce the intensity or frequency of seizures. In the area of behavioral neurotoxicology we are studying the behavioral effects of exposure to heavy metals, insecticides, and environmental toxins both in adult and developing animals. We have developed a battery of behavioral tests that we are continuing to improve and expand. FUNCTIONAL BASES OF MENTAL ACTIVITY Thalía Harmony, Ph.D. Professor thaliah@servidor.unam.mx RELEVANT PUBLICATIONS: Ph.D. Centro Nacional de Investigaciones Científicas, Havana, Cuba, 1969. We look for the characteristics of brain electrical activity that may be related to specific psychological processes involved in different mental tasks. We study the changes in the spontaneous electroencephalographic (EEG) activity that are produced during the performance of specific tasks. As an example, one of the mental tasks that has been explored is mental calculation. It was observed that specific EEG frequencies were associated with different psychological processes. Event Related Potentials (ERPs) are also analyzed under different conditions within a single experiment. Currently, there are two experiments in progress. In one of them we study the ERP components related to behavioral inhibition. In the other experiment those ERP components related to reading are evaluated in children with reading disabilities. Our main goal is to establish whether subjects with cognitive deficits show brain electrical activity different from that observed in normal subjects, and if possible, to identify the altered processes. A second area involves the study of brain function in infants with pre- and perinatal risk factors, many of which may affect child development. These risk factors (e.g.hypoxia) may produce brain lesions that are manifested by signs or symptoms such as seizures. In these cases, medical treatment is indicated, but the parents are not always informed with respect to possible developmental problems, nor is the child always referred for early rehabilitation. It is well known that risk factors may cause motor deficits, such as in cerebral palsy, deficits in language acquisition, sensorial deficits such as hypoacusias, and cognitive deficits including inattention and memory failures, all of which lead to learning disabilities. Our goal is to perform a detailed evaluation of the newborn, by clinical and electrophysiological procedures, in order to initiate as soon as possible the neurorehabilitatory treatment following Katona’s method. We want to increase our knowledge of the mechanisms that facilitate or interfere with normal development in order to continue developing new diagnostic and rehabilitation procedures. Fernández T, Herrera W, Harmony T, DíazComas L, Santiago E, Sánchez L, Bosch J, Fernández-Bouzas A, Otero G, Ricardo-Garcell J, Barraza C, Aubert E, Galán L, Valdés P. EEG and behavioral changes following neurofeedback treatment in learning disabled children. Clinical Electroencephalography 34: 145-152, 2003. Fernández T, Harmony T, Fernández-Bouzas A, Silva J, Herrera W, Santiago-Rodríguez E, Sánchez, L. Sources of EEG activity in learning disabled children. Clinical Electroencephalography 33: 160-164, 2002. Fernández T, Harmony T, Silva J, Galán L, Díaz-Comas L, Bosch J, Rodríguez M, Fernández-Bouzas A, Yáñez G, Otero G, Marosi E. Relationship of specific EEG frequencies at specific brain areas with performance. Neuroreport 9: 3681-3687, 1998. Harmony T, Marosi E, Becker J, Rodríguez M, Reyes A, Fernández T, Silva J, Bernal J. Longitudinal quantitative EEG study of children with different performances on a readingwriting test. Electroencephalography and Clinical Neurophysiology 95: 426-433, 1995. Harmony T, Marosi E, Díaz de León AE, Becker J, Fernández Harmony T. Analysis of electroencephalographic maturation. En: E.R. John, T. Harmony, L. Prichep, M. Valdés, P. Valdés (Eds.). Machinery of the mind, Birkhauser, Boston, pp. 360-375, 1990. Group members: Efraín Santiago, Ph.D. Research Associate Héctor Belmont, B.Sc. Technician 35 NEUROPHISIOLOGY OF PERCEPTION AND PRODUCTION OF TIME INTERVALS IN PRIMATES Hugo Merchant, Ph.D. RELEVANT PUBLICATIONS: Merchant H, Battaglia-Mayer A, Georgopoulos AP. Decoding of path-guided apparent motion from neural ensembles in posterior parietal cortex. Experimental Brain Research 2004 (In press). Merchant H, Battaglia-Mayer A, Georgopoulos AP. Neural responses in motor cortex and area 7a to real and apparent motion. Experimental Brain Research 154: 291-307, 2004. Merchant H, Battaglia-Mayer A, Georgopoulos AP. Neural responses during interception of real and apparent circularly moving targets in motor cortex and area 7a. Cerebral Cortex 14: 314-331, 2004. Merchant H, Battaglia-Mayer A, Georgopoulos AP. Functional organization of parietal neuronal responses to optic flow stimuli. Journal of Neurophysiology 90: 675-682, 2003. Merchant H, Battaglia-Mayer A, Georgopoulos AP. Functional properties of neurons in the motor cortex and parietal area 7a during optic flow stimulation. Journal of Neurophysiology 86: 1955-1971, 2001. Group members: 36 Luis Antonio Prado, B. Sc. Technician Associate Professor merchant@inb.unam.mx Ph.D. in Neurosciences, National University of Mexico, Mexico, 1997. Posdoctoral Fellow, Brain Sciences Center – University of Minnesota, Minneapolis, MN. USA, 1997-1999. Interval timing is a complex process that is involved in a broad spectrum of behaviors, ranging from object interception and collision avoidance to musical performance and speech. In our laboratory we are interested in determining the neurophysiological basis of time estimation in the corticothalamic-basal ganglia circuit of primates. For this purpose Rhesus monkeys will be trained in three tasks: an interval categorization task and production tasks of single or multiple intervals. The timing behavior in monkeys will be characterized using psychophysics techniques, and it will be compared with the capabilities of human subjects to perceive and produce time intervals. The impulse activity of single cells will be recorded during task performance in different areas of the corticothalamic-basal ganglia circuit. The data will be analyzed using statistical methods to correlate timing behavior and single cell and population activity. This will allow us to elucidate the role of corticothalamic-basal ganglia circuit components in the temporal information processing, decipher the neural codes, and reveal the mechanism of interval timing. NEUROCHEMISTRY OF AVERSIVE MEMORY FORMATION: INTERACTION OF THE CORTICAL, LIMBIC AND BASAL CONNECTIONS Isabel Miranda, Ph.D. Assistant Professor miranda@inb.unam.mx Ph.D. Basic Biomedical Research, National University of Mexico, Mexico, 2000. Postdoctoral Fellow, University of California, Irvine, USA, 2002 One of the most outstanding functions of the brain is the memory, without which our capacity to recognize each other and evaluate our environment would disappear. The studies I conduct aim to understand the interaction and the biochemical processes between the different areas involved during memory formation. These studies include behavioral experiments with rats in different learning paradigms, such as conditioning taste aversion. Through this learning, I have been able to conclude that the cholinergic system plays a primary role in the signaling of the novel gustatory stimulus during taste memory formation. Likewise, I have been able to prove that glutamatergic release inside the basolateral amygdala signaling the visceral stimulus that is associated with the previous novel consumption. I am currently developing studies which focus to understand how this interaction between the cortex, amygdala and the basal brain is achieved, what are the neurotransmission systems involved in this communication, and how the hormones released during an aversive event participate during the formation of memories. I am also investigating whether the brain’s mechanisms and structures, which participate in highly emotional memories, are also necessary for the formation of incidental memories. RELEVANT PUBLICATIONS: Miranda MI, McGaugh JL. Enhancement of inhibitory avoidance and conditioned taste aversion memory with insular cortex infusions of 8-Br-cAMP or oxotremorine is disrupted by propranolol infusions into the basolateral amygdala. Learning and Memory 11: 312-317, 2004. Miranda MI, LaLumiere RT, Buen TV, Bermúdez-Rattoni F, McGaugh JL. Blockade of noradrenergic receptors in the basolateral amygdala impairs taste memory. European Journal of Neuroscience 18: 2605-2610; 2003. Miranda MI, Ferreira G, Ramírez-Lugo L, Bermúdez-Rattoni F. Role of cholinergic system on the construction of memories: taste memory encoding. Neurobiology of Learning and Memory 80: 211-222; 2003. Miranda MI, Ferreira G, Ramírez-Lugo L, Bermúdez-Rattoni F. Glutamatergic activity in the amygdala signals visceral input during taste memory formation. Proceedings of the National Academy of Science USA 99: 11417-11422, 2002. Miranda MI, Bermúdez-Rattoni F. Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories. Proceedings of the National Academy of Science USA. 96: 6478-6482, 1999. 37 SEXUAL BEHAVIOR AND PLASTICITY Raúl Paredes, Ph.D. RELEVANT PUBLICATIONS: Paredes RG, Agmo A. Has dopamine a physiological role in the control of sexual behavior? A critical review of the evidence. Progress in Neurobiology 73:179-226, 2004 Portillo W, Basañez E, Paredes RG. Permanent changes in sexual behavior induced by medial preoptic area kindling-like stimulation. Brain Research 961: 10-14, 2003. Paredes RG. Medial preoptic area/anterior hypothalamus and sexual motivation. Scandinavian Journal of Psychology 44: 203-212, 2003. Domínguez E; Portillo W; Baum MJ, Bakker J, Paredes RG. Effect of prenatal androgen receptor antagonist or aromatase inhibitor on the differentiation of neuronal fos responses to estrous female pheromones in the rat accessory olfactory system. Physiology and Behavior 75: 337-346, 2002. Martínez I, Paredes R.G. Only self-paced copulation is rewarding in rats of both sexes. Hormones and Behavior 40: 510517, 2001. Group members: 38 Francisco Camacho, B.Sc. Technician Professor rparedes@servidor.unam.mx Ph.D. in Neurosciences, National University of Mexico, Mexico, 1992. Postdoctoral Fellow, Boston University, Boston MASS., USA, 1992-1994. In recent years our lab has been studying one of the main aspects of reproductive function, sexual behavior. We are interested in identifying the neural circuits that control this behavior, distinguishing brain areas involved in the motivational aspects from those involved in the motor aspects (execution) of sexual behavior. We have also used this behavior to address one of the main questions within Neuroscience: How does the brain produce long lasting changes in its function?. It has been proposed that this neural plasticity can be induced by structural or biochemical modifications that result in permanent changes. In our lab we are evaluating if different models of neural plasticity that induce permanent changes in sexual behavior (and other behaviors as well), do so through similar mechanisms. To induce behavioral changes we use two models: electrical kindling and fetal brain transplants. Kindling is an experimental model of epilepsy in which an initially subconvulsive electrical stimulation of certain brain areas eventually develops into a generalized seizure. Kindling produces long-term neuronal changes that imply widespread modifications of brain function. With fetal brain transplants we evaluate the ability to restore a behavioral deficit produced by the lesion of a specific brain site. We have shown that kindling of the medial preoptic area (MPOA) of the anterior hypothalamus induces sexual behavior in previously non-copulating male rats. The behavioral changes are permanent and appear to be associated with the development of kindling in the MPOA, since kindling in the amygdala fails to induce sexual behavior in non-copulating male rats. We have also shown that fetal brain transplants reestablished sexual behavior in male rats that had lost this capacity after MPOA lesions. The behavioral recovery was associated with the connectivity between the host and the transplanted tissue. We will determine if both models of plasticity induce behavioral changes through the same neuronal mechanisms. NEUROBIOLOGY OF MEMORY Roberto A. Prado-Alcalá, Ph.D. Professor prado@servidor.unam.mx RELEVANT PUBLICATIONS: Ph.D. (Psychology), Concordia University, Canada, 1982 In Dr. Prado´s laboratory the neurobiological bases of memory are studied. One current hypothesis that guides his work states that during the process of memory consolidation there is a transformation from a functional organization in series among several cerebral structures and neurochemical systems into a functional organization in parallel during the final stages of permanent storage of memory. The following are some of the main contributions of his laboratory to the field: a) The systematic study of the protective effect of enhanced learning against experimentally-induced amnesia. So far, we have consistently found that all treatments which produce amnesia become totally ineffective when animals are submitted to strong training. b) The demonstration that the neostriatum participates in memory consolidation of different types of conditioned behaviors. c) Corroboration that other structures closely related to the neostriatum are also necessary for memory formation. d) Identification of some neurotransmitters that are involved in memory storage (e.g., striatal acetylcholine (Ach), GABA, and serotonin). e) Quantification using binding techniques of the synthesis of neuronal Ach receptors that occurs after learning. We have found an up-regulation of Ach receptors in the striatum, hippocampus, amygdala, substantia nigra and neocortex. Current goals of this laboratory are: further “mapping” of the brain, in search of regions or nuclei that may share functional characteristics with the neostriatum; to study possible functional interactions among those structures known to participate in memory consolidation; to determine the basic processes underlying the consolidation of memory. Ongoing experiments deal with morphological changes at the level of dendritic fields, as well as possible changes in the density of several membrane receptors and synaptic vesicles, as a consequence of different levels of learning. These experiments utilize both conventional methodologies (e.g., behavioral, pharmacological, photonic microscopy) and state-of-the art techniques (e.g., confocal microscopy, immunohistochemistry, microarrays). Prado-Alcalá RA, Ruiloba MI, Rubio L, SolanaFigueroa R, Medina C, Salado-Castillo R, Quirarte GL. Regional infusions of serotonin into the striatum and memory consolidation. Synapse 47: 169-175, 2003. Prado-Alcalá RA, Solana-Figueroa R, Galindo LE, Medina AC, Quirarte GL. Blockade of striatal 5-HT2 receptors produces retrograde amnesia in rats. Life Sciences 74: 481-488, 2003. Quiroz C, Martínez I, Quirarte GL, Morales T, Díaz-Cintra S, Prado-Alcalá RA. Enhanced inhibitory avoidance learning prevents the memory-impairing effects of posttraining hippocampal inactivation. Experimental Brain Research 221: 400-402, 2003. Martínez I, Quirarte GL, Díaz-Cintra S, Quiroz C, Prado-Alcalá RA. Effects of lesions of hi-ppocampal fields CA1 and CA3 on acquisition of inhibitory avoidance. Neuropsychobiology 46: 97-103, 2002. Prado-Alcalá RA. Serial and parallel processing during memory consolidation. In: Plasticity in the Central Nervous System. Learning and Memory. McGaugh, J. Bermúdez-Rattoni, F., Prado-Alcalá, R.A. (Eds.), Lawrence Erlbaum Publishers, New Jersey, pp. 57-65, 1995. Group members: Cristina Medina, Ph. D. Technician 39 NEUROBIOLOGY OF LEARNING Gina Quirarte, Ph.D. RELEVANT PUBLICATIONS:. Prado-Alcalá RA, Ruiloba MI, Rubio L, SolanaFigueroa R, Medina C, Salado-Castillo R, Quirarte GL. Regional infusions of serotonin into the striatum and memory consolidation. Synapse 47: 169-175, 2003. Roozendal B, Quirarte GL, McGaugh JL. Glucocorticoids interact with the basolateral amygdala β-adrenoceptor-cAMP/PKA system in influencing memory consolidation. European Journal of Neuroscience 15: 553-560, 2002. Quirarte GL, Gálvez R, Roozendaal B, McGaugh JL. Norepinephrine release in the amygdala in response to footshock and opioid peptidergic drugs. Brain Research 808: 134-140, 1998. Quirarte GL, Roozendaal B, McGaugh JL. Glucocorticoid enhancement memory storage involves noradrenergicv activation in the basolateral amygdala. Proceedings of the National Academy of Sciences USA 94: 14048-14053, 1997. Quirarte GL, Cruz Morales SE, Díaz del Guante MA, García M, Prado-Alcalá RA. Protective effect of under-reinforcement of passive avoidance against scopolamine.induced amnesia. Brain Research Bulletin 32: 521-524, 1993. Group members: 40 Norma Serafín, B.Sc. Technician Assistant Professor ginaqui@servidor.unam.mx Ph.D. in Physiology, National University of Mexico, Mexico, 1995. Postdoctoral Fellow. University of California, Irvine, CA, USA. 1995-1996. A main goal in neurosciences is to understand the brain mechanisms involved in learning and memory. It is known that not all experiences are equally remembered, and some evidence indicates that emotionally charged events tend to be better recalled; in general, the strength of memory reflects the meaning of those events. There are data that support the hypothesis that emotional responses modulate long-term memory storage. The focus of our laboratory is to test this hypothesis experimentally. To this end we use two aversively-motivated learning tasks: inhibitory avoidance and the water maze. There is evidence indicating that adrenal hormones and some neurotransmitters, such as acetylcholine, noradrenaline, and serotonin, are involved in learning these tasks. We are currently studying how adrenal hormones and neurotransmitters interact with each other during learning. These hormones have been extensively studied in regard to the amygdala and hippocampus, but not in relation to the striatum. The striatum is part of the basal ganglia, participates in memory consolidation, and has glucocorticoid receptors, which are sensitive to adrenal hormones. These characteristics have led us to study the possible involvement of striatal glucocorticoids in memory of aversive experiences. Some of the experimental techniques used in our laboratory include: behavioral testing, stereotaxic surgery, intracranial and systemic administration of drugs, and histological analyses (light, confocal and electron microscopy). PLASTIC NEURAL NETWORKS AND ITS ROLE IN COGNITION Victor Ramírez-Amaya, Ph.D. Assistant Professor ramirez@inb.unam.mx Ph.D. Biomedical Research, National University of Mexico, Mexico,. 1999. Posdoctoral Fellow: Instituto de Fisiología Celular, National University of Mexico, Mexico,. 2000-2002; Neural Systems Memory and Aging, The University of Arizona. 2002-2005. Learning a new behavior and acquiring information from the environment requires a dynamic set of cellular events in neurons from different regions of the central nervous system. Coordinated neural activity, regulation of gene expression and protein activity are cellular events that underlie plasticity in neurons. Neural plasticity modify the status of the neural network by changing the efficiency of synapses, their structure, the distribution and amount of synaptic contacts, and even the genesis of new neurons. Plasticity is required to establish a neural representation of the stimulus in form of neural ensembles, whose coordinated activity will ultimately represent the acquired information and maintain it as long-term memory. We study the behavioral activation of specific neural groups along the CNS, particularly in regions important for learning and memory such as the hippocampus and the cortex, among other regions. We track cellular events, such as the activation of genes (Arc, Homer1a, Zif268, cFOS, BDNF, etc.) and the translation and phosphorilation of proteins (CREB, CAMKII, etc.) during learning acquisition and memory formation. We use catFISH (compartamental analysis of temporal activity using fluorescence in situ hybridization) combined with fluorescence immunohistochemistry to identify these molecules in specific groups of cells (we can also identify the cell type) after the animals underwent a particular behavior. We are also combining these methods with those that detect new born neurons to study neurogénesis and we are trying to combine it with strategies to study the fine structure of dendrites, using confocal microscopy. By investigating the induction of genes and the regulation of proteins after the acquisition of a learning task (such spatial learning or classical and operant conditioning), we want to understand the dynamic interactions among these cellular events and how they lead to sinaptogenesis and neurogenesis. These plastic events in neurons are of particular interest because it is believed that they underlie the formation of memories. RELEVANT PUBLICATIONS: Chawla MK, Guzowski JF, Ramirez-Amaya V, Lipa P, Hoffman KL, Marriott LK, Worley PF, McNaughton BL, and Barnes CA. Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience. Hippocampus 15: 579-86, 2005. Ramírez-Amaya, V, Vazdarjanova A, Michael D, Rosi S, Worley PF, Barnes CA. Spatial Exploration-Induced Arc mRNA and Protein Expression: Evidence for Selective, NetworkSpecific Reactivation. Journal of Neuroscience 25: 1761-1768, 2005. Rosi S, Ramirez-Amaya V, Vazdarjanova A, Hauss-Wegrzyniak B, Worley PF, Barnes CA, and Wenk GL. Neuroinflammation Disrupts the Pattern of Behaviorally Induced Arc Expression in the Hippocampus. Journal of Neuroscience 25: 723-731, 2005. Ramirez-Amaya V, Balderas I, Sandoval J, Escobar ML, Bermudez-Rattoni F. Spatial long-term memory is related to mossy fiber synaptogenesis. Journal of Neuroscience 21:7340-8, 2001. Ramírez-Amaya V, Escobar ML, Chao V, Bermúdez-Rattoni F. Synaptogenesis of Mossy Fibers Induced by Spatial Water Maze Overtraining. Hippocampus 9:631-636, 1999. 41 The Institute of Neurobiology offers two graduate programs whose main objective is to introduce the student to the fundamental aspects of contemporary neurosciences and, starting from there, to prepare him/her to become an independent thinker, a specialized expert, and a master technician in certain areas. Similarly, by undertaking graduate studies toward a master’s or doctoral degree, highly motivated researchers acquire an integral understanding of the functioning of the nervous system, leading to an increase in the number of scientists working in this field. GRADUATE STUDIES AND SCIENCE AWARENESS PROGRAMS In INB one can study toward a Master of Science (Neurobiology) degree or a Doctorate in Biomedical Sciences. In these programs the student specializes in the nervous system through formal courses and seminars and at the same time he/she starts an original research project under the close supervision of a faculty mentor. For this, INB has a teaching and research staff, who belong to the National Scientific Research system (SNI) and are acknowledged at national and international levels. INB has modern and spacious facilities and fully-equipped laboratories to carry out research with international standards. Based on their quality and level of scientific production, both programs have been assessed and certified as “competent at international level” by the National Postgraduate Census of the National Council of Science and Technology (CONACyT), and as a consequence, students have access to scholarships, provided they comply with the requirements of the public announcement Graduate Study Programs: Duration: Commitment: Modality: Entrance: Web: Master of Science (Neurobiology) 4 semesters Full time Attend courses and design and carry out a research project Annual www.inb.unam.mx Doctorate in Biomedical Sciences 8 semesters Full time Research project Semi-annual www.pdcb.unam.mx Scholarship Programs 44 • Probetel: This scholarship program is intended to support research projects leading to an undergraduate thesis and degree. Students having completed 85% of the course and with an average grade of 8.5 are eligible to start working on his/her thesis research in any of the lines developed in INB and to apply for financial support to undertake such activity. • Every six months, CONACyT issues a public announcement offering the National Scholarships for the Investment in Knowledge. Students registered in any of the programs pertaining to the National Graduate Programs Catalog, having an undergraduate degree, and 8 as an average grade may compete for these scholarships. • The UNAM, via the General Direction of Postgraduate Studies, offers scholarships for Master’s or Doctoral studies. To obtain this kind of support, the stu- dent must have 8.5 as a minimum average grade and be registered in any of the postgraduate programs offered by UNAM. In addition, INB offers training programs for human resources including, among others, the research and writing required to prepare a thesis, summer research visits, social service, as well as courses in various specialties and new, cutting-edge fields and techniques. Programs for the Popularization of Science: Guided tours of INB are intended for various educational levels –elementary, high school, and university– as well as other special interested groups (Thursdays). Institutional Seminars (12 o’clock on Fridays) Brain Awareness Week (March of each year) Research Visits: These take place from June to August with the following aims: a) To facilitate the interaction between researchers and those students having a scientific vocation; b) To motivate students to incorporate scientific research into their academic endeavor, and c) To promote graduate studies. Participating Programs: • • • • • Science Summers in the Central Region (Verano de la Ciencia Región Centro,) Summer of the Mexican Academy of Science (Verano de la Academia Mexicana de la Ciencia) Summer in the Pacific Region (Verano de la Región Pacífico, Delfín) Youngsters in Research, UNAM (Jóvenes a la Investigación) Minority Health and Health Disparities International Research Training Program (MHIRT), under the auspices of the University of California. Further information: Leonor Casanova, B.Sc. Tel: +[52] (442) 238 10 16 or (55) 5623 40 16; FAX: +[52] (442) 238 10 17 or (55) 5623 40 17 e-mail: posginb@servidor.unam.mx www.inb.unam.mx www.pdcb.unam.mx 45 The Institute of Neurobiology has developed a research program on the early diagnosis of brain lesions in newborns and infants due to prenatal and/or perinatal causes, as well as implemented neurohabilitation therapies to counteract incapacitating sequels. This program is directly linked to a public health problem of large but unknown dimensions and therefore has an important social impact. NEURODEVELOPMENT RESEARCH UNIT Thalía Harmony, Ph. D. Antonio Fernández Bouzas, Ph. D. Thalía Fernández, Ph. D. Efraín Santiago, Ph. D. Josefina Ricardo, Ph. D. 48 In Mexico, the National Institute of Statistics, Geography, and Informatics has determined that approximately 19% of all disabilities are related to prenatal or perinatal problems. Nearly 10% of births in our country are associated with risk factors underlying brain damage, and from these, 5% actually suffer some type of severe lesion or dysfunction with consequences for motor (infant cerebral paralysis), sensory (hypoacusia) and/or cognitive (attention deficit disorder, learning disabilities, language retardation, among others) development. When brain damage is diagnosed early and a convenient neurohabilitation therapy is initiated immediately, it is possible to prevent or reduce in a significant manner the incapacitating consequences or sequelae caused by such a lesion. The aims of the Neurodevelopment Research Unit (UIND, initials in Spanish) of the INB are to develop new and sensitive diagnostic methods for the early detection of brain lesions, as well as to evaluate therapeutic procedures applied immediately after birth (to take the maximum advantage of brain plasticity mechanisms present during early postnatal life) that can reduce or prevent motor, sensory, and/or cognitive sequels and have proven efficacious in reducing the incidence of disabilities produced by neonatal brain damage. Some of the diagnostic procedures utilized in the UIND for the assessment and follow-up studies of infants with brain lesions are: magnetic resonance neuroimaging (MRI), cerebral flux ultrasound (US), electroencephalographic (EEG) mapping, and auditory and visual evoked potentials. Similarly, the neurohabilitation therapy developed by Professor Ferencz Katona in Hungary is applied; this therapy is based upon vestibular stimulation obtained by placing the head in different positions, producing a series of complex movements that occur only in humans. The intensive repetition of the exercises of this therapy and the subsequent provoked stimulations constitute an effective training for the brain to create a normal or adequate motor development. Moreover, this diagnostic methodology and other clinical tests are used to assess whether neurohabilitatory therapies are capable of preventing or reducing incapacitating sequels of brain damage. The potential benefits of this research program are, among others, the following: • Consolidation of a multidisciplinary group focused on the development of effective programs using early intervention to help reduce the incidence of incapacitated individuals by diminishing the sequelae of brain lesions acquired prior to or during birth. • Currently there are no institutions that specialize in treating children with brain lesions during their first months of life, when the brain plasticity mechanisms are most active. In fact, the typical rehabilitation programs are less effective, because they are normally initiated late in development, when such mechanisms are reduced. • Neurohabilitated children will have a better quality of life –personal, family, and social. This will have a deep impact on their scholar/laboral development and hence on their social/economic level. • Early preventive treatment is much more efficient and less expensive than the late treatment of disabilities. Therefore, health and economic benefits exist in both the family and social fields when these children are treated early in their lives. • To develop research and new insights into the area of brain plasticity, as well as to find new methods of prevention, diagnosis, and treatment for brain lesions. • To train specialized professionals in these areas who will have an impact in the health, education, and social sectors. • The successful application of this method in Queretaro will facilitate the spread of such programs to other regions of the country (and eventually to other countries), amplifying their impact and reaching wider populations of children born with these problems. 49 The Institute of Neurobiology includes various core facilities in which high-technology equipment and instruments are concentrated, together with qualified personnel to provide assistance to all research groups on the application of sophisticated techniques and methodologies, which are generally quite expensive. Furthermore, these Units offer advice on conceptual views to explore alternate approaches to diverse research problems; they also provide courses that up-date the academic staff and students of the Institute and train them in the use of special techniques. These Units also offer their services to external users, and in so doing they help widen the impact of INB on the region, as well as to draw extra income into the institution. Research Support Units in INB are: • Digital Image Analysis Unit • Molecular Biology Unit • Analytical Biochemistry Unit • Electron Microscopy and Histology Unit • Magnetic Resonance Unit IMAGE ANALYSIS UNIT Fernando Barrios, Ph. D. Nydia Hernández, B.Sc. Leopoldo González, M.Sc. The Digital Image Analysis Unit (UAID, initials in Spanish) has equipment and systems related to capture, filtering, processing, and feedback procedures for the analysis of practically any type of digital image that can be transferred to computational systems. This Unit offers technical support in the following areas: a) FLUORESCENCE AND PHASE CONTRAST MICROSCOPY. The instrument is a Nikon E-600 equipped with two cameras, one for 135 mm film and a high resolution, high sensitivity digital camera connected to a computing system having a IPLab image analysis program that also controls the motorized microscope stage (XY) and focus control (Z), as well as a fluorescence filter wheel for automatic exposure acquisitions controlled by the analysis system. b) CONFOCAL SCANNING MICROSCOPY The instrument is a Nikon E-600 coupled to a confocal scanning system Nikon PCM 2000 with two lasers, HENE (543 nm) and argon (488 nm), and computational equipment for capturing images, sequence control, and image feedback in TIF format, using Simple PCl software. c) IMAGE DIGITIZATION. This is carried out with a high resolution scanning method to digitize images from slides, radiographs, and gels. Quantitative analysis can be undertaken for every type of digital image with the use of specialized programs such as: IPLab, NIHImage, EDL, Gel IPLab, ImageL, among others. d) PREPARATION OF POSTERS AND SPECIAL TEXTS. Assistance provided to research scientists, technicians, and students in the use of diverse software to create posters, articles, presentations, and animations and to manipulate files such as proofs in pdf format. e) HIGH QUALITY COLOR PRINTS. This is done with a Tektronix Phaser 750 printer, as well as with Palette equipment for slide printing. 52 MOLECULAR BIOLOGY UNIT Alfredo Varela-Echavarría, Ph. D. Anaid Antaramián, Ph.D. The aims of the Molecular Biology Unit (UBM, initials in Spanish) are to provide sophisticated experimental services such as automated DNA sequencing and RNA quantification using real time PCR, as well as to supply materials and assistance in general methodologies concerning molecular biology and special techniques convenient for the users’ needs. With the purpose of giving special attention to those persons with no experience in molecular biology, but who wish to enter this field in order to solve specific questions arising from their research projects, UBM offers the following services: a) AUTOMATIC DNA SEQUENCING, with an ABI Prism 310 Genetic Analyzer instrument of one capillary, capable of sequencing approximately 600 nucleotides per reaction. b) REAL TIME PC, with a Light Cycle Roche instrument that allows the quantification, with high sensitivity and reproducibility, of the expression of diverse mRNAs. c) ANALYSIS OF RADIOACTIVE OR CHEMILUMINESCENT SAMPLES. A Molecular Dynamics Storm 860 instrument is used to detect, with high sensitivity, light, fluorescent, or radioactive signals. d) PRODUCTION OF MATERIALS. The UBM routinely produces the following materials required in molecular biology methodologies for the different laboratories: competent Escherichia coli cells for transformation; liquid LB medium, and LB medium in Petri dishes with and without antibiotic. e) TECHNICAL ASSISTANCE. The Unit offers theoretical and practical assistance on the possible benefits that diverse techniques in molecular biology may render to the various projects carried out in the Institute of Neurobiology, including, in addition to those mentioned above: in situ hybridization; bacterial electroporation; in ovum electroporation for the ectopic expression of proteins of interest in the different chicken embryonic regions; bacterial transformation; cloning; normal PCR; Southern blots, etc. f) SPECIAL COURSES: The UBM offers a course on INTRODUCTION TO MOLECULAR BIOLOGY for internal and external users. 53 ANALYTICAL BIOCHEMISTRY UNIT Manuel Aguilar, Ph.D. Aurelio Rodríguez, B.Sc. The Analytical Biochemistry Unit (UBA, initials in Spanish) offers the academic community a series of instruments and services to isolate and purify peptides and proteins, as well as to characterize their structural properties. UBA provides the following assistance: a) AUTOMATIC PROTEIN SEQUENCING by degrading the protein from its amino terminus using the Edman method and the ABI Procise 491 Protein Sequencer, which can use protein samples provided in solid or dissolved form or transferred to PVDF membranes. b) ISOLATION AND PURIFICATION OF PROTEINS. These procedures are carried out using three HPLC instruments with capability of binary, tertiary, and quaternary gradients and with diverse detectors (UV, visible, and electrochemical) as well as two FLPC instruments and conventional chromatography systems including gel filtration, ion exchange, chromatic focusing, reverse phase, and affinity chromatography. c) PROTEIN CHARACTERIZATION TECHNIQUES. These include various electrophoretic analyses (native gels, denaturing gels, isoelectric focusing); relative molecular mass determination; amino acid analysis and composition; determination of carboxy-terminal sequences, disulphide bridge characterization; amino acid chemical derivation; protein enzymatic analysis and “fingerprint” studies. d) RADIOACTIVE LABELING OF PEPTIDES AND PROTEINS with the isotope 125I to prepare tracer samples for radioimmunoanalysis or receptor assays. e) TECHNICAL ASSISTANCE, UBA provides practical and theoretical assistance to internal and external users on various protein biochemistry techniques to further the development of the projects in the Institute. 54 ELECTRON MICROSCOPY AND HISTOLOGY UNIT Alfonso Cárabez-Trejo, Ph.D. Lourdes Palma, B.Sc. Evelyn Flores, Tech. The Electron Microscopy and Histology Unit (UMEH, initials in Spanish) provides assistance in the morphological and ultrastructural analysis of diverse biological samples, ranging from the tissue and cellular levels to the subcellular scale, employing light and scanning electron microscopy techniques. In general, technical assistance and support is provided for the processing of samples needed in the corresponding microscopic analyses (fixation, dehydration, paraffin inclusion, block preparation, cutting and mounting) and the development of the different staining techniques for histochemistry and immunocytochemistry, as well as for ultrastructural analysis using transmission and scanning electron microscopy (fixation, inclusion in special resins, negative staining, and shadowing of samples). This unit has the following equipment to carry out its functions: a) Transmission electron microscope, JEOL JEM 1010 model, for diverse ultrastructural analyses at cellular and subcellular levels, with a magnification power up to 500 000X. b) Ultramicrotome, RMC MTX model, for thin and semi-thin sections to be analyzed under the electron microscope. c) Evaporator of metals and metalloids, JEOL JEEE400, for the processing and contrasting of samples for electron microscopy. d) Dehydrator or histokinete, Leica TPRO20, for the preparation of samples for histological analysis. e) Instrument for paraffin embedding of tissue, Leica EG1 160, for the preparation of blocks with pre-fixed tissue. f) Microtome for paraffin blocks, RM2 135, for the preparation of histological sections of various thicknesses. g) Heating plate for deparaffination, Leica H1 1210, to remove paraffin from the tissue sections and allow the application of various dyes to the sections under study. 55 MAGNETIC RESONANCE UNIT Thalía Harmony, Ph. D. Antonio Fernández-Bouzas, Ph.D. Fernando Alvarez, Ph.D. Angel Romero, M.D. Juan José Ortiz, M.Sc. David Avila, Tech. Radiol The Magnetic Resonante Unit (MRU) has the following objectives: 1) Attention to the infant population with pre- and perinatal risk antecedents indicating the possibility of neurological damage in the State of Queretaro and neighboring regions; 2) Development of various research projects by the academic staff of the INB; 3) Training of specialized personnel; and 4) Neuroimage diagnosis services for patients of both the public and private health sectors, to foster the social integration of the Institute with the community and, simultaneously, to obtain extra income to cover the operation and maintenance of the equipment in this Unit. At the present time, the MRU has the following equipment: a) A Phillips Magnetic Resonator Gyroscan Intera of 1.0 Tesla, with the following components: a new and revolutionary ultra compact superconductor magnet actively protected, a powerful system of Stellar gradients, Flex Sense coils for skull and spinal cord, and the latest version of clinical imaging software (Scantools version 10) developed by Phillips. With this equipment it is possible to carry out, all of the conventional studies –T1W, T2W, and Proton Density–, as well as other techniques such as FLAIR and TURBO that perform short time sequences and diffusion and perfusion techniques that are very useful for the study of circulatory alterations and cerebral vascular lesions. Furthermore, other studies like angioresonance of intracranial vessels can be performed, with and without contrasting medium injection, and there is the possibility of spectroscopic techniques for the analysis of biochemical alterations in pathological or supposedly normal areas. b) A Digital high precision injector (MedRed) that enables the synchronization of image acquisition with the flux of the contrast medium in the region of interest. c) Ultrasound Doppler transcranial equipment, by Phillips, for the performance of detailed cerebral flux studies. 56 The Magnetic Resonance Unit employs expert and qualified neuroradiologists to perform and interpret the studies, as well as highly trained technicians for optimal handling of the equipment. Information for appointments is available at the phone numbers (442)238-1078 and (442)238-1079. The Institute of Neurobiology also has the support of Units that provide basic services for routine operation. The personnel and equipment of these Units carry out their work in a professional and efficient manner to ensure that the activities of the Institute are performed in optimal conditions. The Academic Service Units of the INB are: • Library • Vivarium • Computing Unit • Teaching Unit • Photography and Drawing Unit • Videoconference Unit LIBRARY Ma. del Pilar Galarza, B.Sc. The Library of the INB continuously acquires periodical publications, books, and theses. The total stock consists of 94 collections of journals specialized in neurosciences (total of 11,500 issues), 4,980 books, 520 theses, and 317 compact disks. SERVICES A series of support services are carried out both for the academic community and external users consisting of: a) HOME LOANS OF MATERIALS. b) INTERLIBRAY BOOK LOANS. c) INTERNAL DOCUMENTATION SERVICE: To retrieve articles or book chapters requested by the academic and postgraduate communities of the INB, applications are processed to recover the information from several institutions in Mexico and abroad. d) CITATION ANALYSIS OF SCIENTIFIC PRODUCTIVITY: The unit assists researchers with grant applications by assembling citations using the WEB of SCIENCE and DIALOG systems. e) ASSISTANCE TO USERS EXTERNAL TO THE INSTITUTE: In addition to the personnel and students of the INB, the Library provides services to users from the following institutions: UAQ, UNAM, UVM, CINVESTAV, other educational institutions of the State of Queretaro and other regions of the country. f) ALERT BULLETIN: Bulletins are written and sent by electronic mail to all the academic and postgraduate communities of the INB, with information related to recently acquired books, instructions about the use and handling of data bases, and news and general information about scientific and cultural activities. 58 VIVARIUM José Martín García, D.V.M. The Vivarium of the INB is constituted as an entity for the production and care of biological models (Laboratory Animals for Experimentation). The production goes mainly to meet the internal demands, with twenty laboratories of the institute itself as consignees of this service, as well as external users that include other academic entities of UNAM and other local and national university institutions. PRODUCTION OF LABORATORY ANIMALS The vivarium breeds rats of the following strains: Wistar (6,500), Sprague Dawley (2,000), and Lewis (100), as well as mice of the line C57BL/6 (250) and strain CD-1 (1,500) (the approximate number of animals per year is indicated in parentheses). The breeding systems employed are the Modified Monogamous Pair Circular and the Polygamous (harem); with these and through reproductive records, it has been possible to maintain the genetic quality of the species. The vivarium is provided with the facilities and procedures that guarantee the necessary conditions of hygiene, health, and microbiological and parasitological controls to produce experimentation animals with a high biological quality. CARE OF LABORATORY ANIMALS In addition to the species that are produced in the vivarium, this facility hosts live species acquired from other vivariums and breeders, such as GAHER rats (imported from France), Balb/c mice, New Zealand rabbits, chickens, Xenopus frogs, turtles, and fish. 59 COMPUTING UNIT Alberto Lara, M.Sc. Omar González, B.Sc. The Computing Unit (CU) administers and maintains the computing and telecommunication resources of the Institute, and it gives assistance to internal and external users. The INB currently has available 3 SUN Servers, 4 Silicon Graphics Workstations, 40 Macintosh, and 200 PCs, 90% of which are connected via the LAN network of the Institute through an optic fiber link to RedUNAM, and therefore to the Internet. More than 20 of these computers control high performance instruments such as HPLCs, multi-channel EEGs, microscopes –electronic, confocal, and fluorescence– and digital cameras, among others. Additionally, INB has 7 high- capacity printers connected to the LAN network and 110 printers connected to computers that can be shared with others within the internal network. This network is formed by a 1 Gbps optic fiber backbone, 7 switches, 10/100Mbps and 15 10Mbps concentrators distributed in the 6 buildings and a 10Mbps optic fiber connection with the main switch at the telecommunications building of the Juriquilla Campus. SERVICES TO USERS The following services provided by the CU are, among others: • Installation, configuration, or reconfiguration of software • Assistance and technical support to PC users: Graphics, Statistics, Reports to CONACYT and SNI, Optimization of Files and Programs, Elimination of viruses. BLIND SEVICES The Unity provides a series of maintenance and modernization services of the voice and data network that include: Telephony and Network. TECHNOLOGY 100Mbps network cards have been installed, with which the information transmission speed was increased by a factor of 10. 60 TEXT EDITING IN ENGLISH Dorothy Pless, Ph.D. The Institute has the assistance of Dr. Dorothy Pless to correct or improve the style of scientific texts in English to insure that they comply with correct grammar and idiomatic structure. PHOTOGRAPHY UNIT The Photography Unit of the Institute of Neurobiology offers the following services: BLACK AND WHITE PHOTOGRAPHY: The service includes photographing and developing scientific material for publication with a high quality reflex camera. SLIDES: The service includes slide processing with a reflex camera, or with a Palette Digital Polaroid HR6000 from files provided by the users. DIGITAL PHOTOGRAPHY: The service includes processing of photographs with a high resolution (more than 6 Mega pixels) digital camera, improvement of the images, and their recording in CD (provided by the user) or the transmission of the corresponding files through e-mail. The files are submitted in standard format, portable in different platforms. In addition, this Unit is in charge of the visual and photographic recording of the diverse activities taking place in the Institute and Campus, such as: cultural events, institutional seminars, official activities, and academic events like the “Jornadas del Instituto de Neurobiología” held annually to commemorate the anniversaries of the INB, photographs of the graduating students and academic and technical staff. 61 VIDEOCONFERENCE UNIT Ma. de Lourdes Lara, B.Sc. Audio and video transmission is carried out in the Videoconference Unit (VCU), in an interactive way, covering diverse events taking place in academic entities at main campus in Mexico City and other universities and research centers of the country and abroad. The purpose of the Videoconference Unit of the INB is to provide assistance to the academic staff and post-graduate students (Master’s and PhD) in teaching and collaborative activities. The up-to-date technology of this Unit provides the interactive transmission and reception, in real time, of audio and video of various events organized on the main campus of the University of Mexico, as well as at other national and international universities and research centers. The Videoconference Network of UNAM maintains links through optical fiber and satellite with more than 93 videoconference rooms throughout the country as well as with international sources. In this way, activities such as courses, workshops, seminars, conferences, academic meetings, and tutorial or degree exams can take place at the INB facilities and include participants at other locations; likewise, events at other institutions can be brought to INB, both of which represent great advantages. The VCU also provides support to the Administration to conduct meetings, to provide courses to update administrative personnel and to support other centers of the Juriquilla Campus of the UNAM. SUPPORT TO THE GRADUATE PROGRAMS With the increasing number of students, more tutorial, master’s degree, and PhD candidate exams utilize this medium. This service also transmits the meetings of the Academic Committee for the Doctorate in Biomedical Sciences with representatives of the INB itself. Likewise, courses given at UNAM facilities on its main campus in Mexico City are transmitted as part of the program of optional courses of the Doctorate in Biomedicine Sciences or of the Master’s in Neurobiology. SUPPORT TO THE DIRECTION OF INB Linkages are supplied for the working meetings of the Scientific Research Technical Council and other extraordinary Special Commissions and the Academic Councils of Area. SUPPORT TO UNAM AND EXTERNAL ENTITIES Popularization of science conferences, as well as courses given by other research centers of the Campus or other regional institutions are video transmitted. 62 INB IN NUMBERS ACADEMIC STAFF The Institute of Neurobiology has a staff of 94 members, distributed as follows: 51 Researchers: 43 Academic Technicians (T.A.) 1 Emeritus Professor 4 Senior T.A., level “C” 1 Extraordinary Professor 3 Senior T.A., level “B” 11 Professors 14 Senior T.A., level “A” 7 Associate Professors 16 Associate T.A., level “C” 12 Assistant Professors 2 Associate T.A., level “B” 13 Research Associates 4 Technicians assigned to projects 6 Postdoctoral Fellows SCIENTIFIC PRODUCTIVITY INB scientific productivity for the period 1993-2004 consists of 620 publications in the following categories: 452 original research articles 101 chapters in books 20 books 47 extended reports GRADUATE STUDENTS INB academic staff has graduated 233 students in their respective teaching programs, and through the supervision of research theses for the various degrees: 65 doctoral degrees 86 master’s degrees 82 bachelor’s degrees AWARDS INB academic staff has received various prestigious acknowledgements for scientific contributions; among these we can mention: • National Award for Sciences and Arts 1996 (Physics-Mathematics and Natural Sciences Area). • National University Award for Young Scientists 1995 and 2004, Natural Sciences Area. • Príncipe de Asturias Award, 1999. • National University Award for Teaching in the Natural Sciences Area, 2000. 63 LOCATIONS OF NATIONAL AUTONOMOUS UNIVERSITY OF MEXICO CAMPI 64 This city is located 220 km from Mexico City in the central zone of the Mexican Republic. Since 1996, it has been a World Heritage City. Two events fundamental for the history of the Mexican Nation were incubated in this city, the conspiracy movement leading to Independence and the promulgation of the Constitution of the United Mexican States. Given its geographical location, it is the access route to the northern part of the country; its population consists of almost a million inhabitants. Beyond its architectonical beauty and historical wealth, the city hosts branches of the main teaching institutions of the country, as well as of diverse cultural foundations and institutions, including the Queretaro State Philharmonic Orchestra and art and history museums. www.queretaro.gob.mx DIRECTORY Mexico code (+52), Queretaro (+442) Director’s Office Academic Secretary Administration Graduate Programs MRI Unit 238•1001 238•1002 238•1009 238•1016 238•1079 fax 238•1004 238•1005 238•1017 STAFF 66 Aceves Carmen Aguilar Manuel Anguiano Brenda Arámburo Carlos Arellano Rogelio Barrios Fernando Carábez-Trejo Alfonso Cintra León F. Clapp Carmen Condés-Lara Miguel Díaz Sofía Díaz-Muñoz Mauricio Duran Pilar Fernández-Bouzas Antonio Fernández Thalia Fiordelisio Tatiana Flores Marcos García-Colunga Jesús Giordano Magda González Ma. del Carmen Granados Leticia Harmony Thalia Heimer Edgar P. Jeziorski C. Michael Larriva-Sahd Jorge Luna Maricela Martínez Minerva Martínez de la Escalera Gonzalo Martínez-Torres Ataúlfo Mejia Carmen Mena Flavio Merchant Hugo Miledi Ricardo Miranda Isabel Morales Teresa Morales Verónica Ochoa Lenin Orozco Áurea Paredes Raúl Pérez Esther +52 (442) caracev@servidor.unam.mx maguilar@servidor.unam.mx anguiano@inb.unam.mx aramburo@servidor.unam.mx arellano@inb.unam.mx barrios@inb.unam.mx carabez1@servidor.unam.mx cintra@servidor.unam.mx clapp@servidor.unam.mx condes@servidor.unam.mx yoldi@servidor.unam.mx mdiaz@inb.unam.mx pilis@servidor.unam.mx fabouzas@servidor.unam.mx thalia@servidor.unam.mx fiordelisiotatia@yahoo.com mflores31@hotmail.com garciac@inb.unam.mx giordano@servidor.unam.mx macastimx@yahoo.com.mx granados@inb.unam.mx thaliah@servidor.unam.mx heimer@servidor.unam.mx jeziorsk@inb.unam.mx jlsneuro@servidor.unam.mx lunam@servidor.unam.mx martinea@inb.unam.mx gmel@servidor.unam.mx ataulfo@inb.unam.mx mejia.e.mejia@uv.es fmena@servidor.unam.mx merchant@inb.unam.mx rmiledi@uci.edu miranda@inb.unam.mx marter@servidor.unam.mx vmorales@ifc.unam.mx lochoa@ifc.unam.mx aureao@servidor.unam.mx rparedes@servidor.unam.mx torrero@biomedicas.unam.mx 238•1067 238•1043 238•1067 238•1065 238•1062 238•1053 238•1031 238•1057 238•1028 238•1042 238•1058 238•1035 238•1057 238•1051 238•1051 238•1071 238•1062 238•1063 238•1061 238•1028 238•1058 238•1051 238•1043 238•1029 238•1030 238•1066 238•1031 238•1002 238•1064 238•1064 238•1070 238•1040 238•1064 238•1039 238•1071 238•1035 238•1064 238•1068 238•1060 238•1059 Prado-Alcalá Roberto Quirarte Gina Ramírez-Amaya Victor Rojas-Piloni Gerardo Salas Manuel Saldaña Carlos Santiago Efraín Valverde-R Carlos Varela-Echavarria Alfredo prado@servidor.unam.mx ginaqui@servidor.unam.mx ramirez@inb.unam.mx piloni@inb.unam.mx masal@servidor.unam.mx csaldana@ifc.unam.mx santiago@inb.unam.mx cavaro@servidor.unam.mx varela@inb.unam.mx Aguilar Azucena Antaramian Anaid Ávila David Belmont Héctor Camacho Francisco Carranza Martha Castilla Alejandra Delgado Guadalupe Falcón Andrés Flores Evelyn Galarza Pilar Garay Edith García Martín González Omar González Leopoldo Hernández Elsa Nydia Lara Lourdes Lara Alberto López-Barrera Fernando Martínez Gema Martínez Irma Martínez Guadaluope Mejia Carmen Mendoza Soledad Nava Gabriel Navarro Nilda Ortiz Juan José Palma Lourdes Peña Teresa Prado Luis Ramos Maria Eugenia Regalado Mirelta Ricardo Josefina Sandoval Francisca Serafín Norma Torrero Carmen Vázquez Olivia Villalobos Patricia aguilar@inb.unam.mx antarami@inb.unam.mx david_avila33@hotmail.com belmont@inb.unam.mx camacho@inb.unam.mx macasa@servidor.unam.mx castilla@inb.unam.mx delgado@inb.unam.mx falcon@inb.unam.mx flores@inb.unam.mx pilargb@servidor.unam.mx edith@servidor.unam.mx garcias@inb.unam.mx ghernan@inb.unam.mx lgs@servidor.unam.mx hrios@inb.unam.mx lulu@servidor.unam.mx lara@inb.unam.mx barreralf@yahoo.com martinec@inb.unam.mx irmaalice@yahoo.com mtzlor@inb.unam.mx mejia@inb.unam.mx solecito75@yahoo.com ganava@excite.com navarro@inb.unam.mx jortiz@slytherin.inb.unam.mx palma@inb.unam.mx pera@inb.unam.mx pradol@inb.unam.mx ramos@inb.unam.mx mirel@servidor.unam.mx oojrg@yahoo.com nserafin@servidor.unam.mx macts@servidor.unam.mx vazquez@inb.unam.mx aguilera@inb.unam.mx 238•1047 238•1047 238•1038 238•1042 238•1059 238•1062 238•1051 238•1068 238•1032 TECHNICIANS 238•1058 238•1034 238•1079 238•1051 238•1060 238•1066 238•1071 238•1067 238•1043 238•1033 238•1019 238•1062 238•1073 238•1052 238•1053 238•1053 238•1015 238•1052 238•1028 238•1030 238•1064 238•1042 238•1032 238•1061 238•1029 238•1071 238•1079 238•1033 238•1069 238•1040 238•1071 238•1059 238•1051 238•1031 238•1047 238•1059 238•1035 238•1068 67 68 Esta publicación se terminó de imprimir en el mes de noviembre de 2005, en los talleres de Diseño e Impresos del Bajío S.A. de C.V. La edición consta de 500 ejemplares. .