Fall 2006 Seminar Series in Neuroscience (Updated 11-10-06)

Dr. David Sweatt Professor; Department of Neurobiology, University of Alabama, Birmingham, School of Medicine

Title:"Epigenetic mechanisms in memory formation"

Abstract: Dr. Sweatt's seminar will focus on molecular mechanisms underlying learning and memory. Dr. Sweatt uses knockout and transgenic mice to investigate signal transduction mechanisms in the hippocampus, a brain region known to be critical for higher-order memory formation in animals and humans. His talk will describe transcriptional regulation in memory formation, focusing on studies of transcription factors, regulators of chromatin structure, and other epigenetic mechanisms, in order to understand the role of regulation of gene expression in synaptic plasticity and memory.

Dr. Ding Xue, Associate Professor; Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder

Title: "Regulation of sexually dimorphic neuronal deaths and drug screens in C. elegans"

Abstract: Sexually dimorphic apoptosis is an ancient and conserved developmental process, in which sex-specific cells or organs (e.g. female-specific Mullerian Duct in mammals) are eliminated in the opposite sex by apoptosis. Misregulation of sex-specific cell deaths could result in severe sexual disorders (e.g., persistent Müllerian duct syndrome). In C. elegans, two sets of neurons undergo sex-specific deaths. Two HSN motor neurons control egg laying in hermaphrodite animals but undergo apoptosis in males where they are not needed. In contrast, four male-specific CEM neurons are speculated to mediate chemotaxis of males towards the hermaphrodite during the courtship process and are programmed to die in hermaphrodites where they are dispensable. The sexually dimorphic deaths of HSNs and CEMs present an excellent paradigm for studying the regulation of neuronal cell deaths and apoptosis signaling pathways. We have employed both genetic and biochemical approaches to identify components that are crucial for sexually dimorphic apoptosis in C. elegans and have identified at least eight different genes that affect only the deaths of HSN or CEM or both but not any other cell death. Molecular genetic and biochemical analyses of these genes and their products suggest that they affect either the transcription or the stability of key apoptosis regulators in sex-specific neurons and thus the sex-specific deaths of these neurons. The studies of sexually dimorphic apoptosis in nematodes will provide important insights into how sexual dimorphism, an ancient reproducing mechanism, is regulated and achieved by appropriate apoptosis and how neuronal cell death is regulated and achieved in general.

Dr. Bob Spencer Associate Professor, Department of Psychology, University of Colorado, Boulder

Title: "Using experience-dependent gene expression to study Stress Neurobiology"

Abstract: A key objective for studying the neurobiology of psychological stress is to identify the neural state(s) that are associated with acute and chronic psychological stress. To tackle this tricky objective we have explored the use of experience-dependent gene expression to “report” on recent changes in the state of brain cells. I will discuss research issues surrounding the psychological “stress-state” concept, and outline our experience-dependent gene expression strategy. I will then share examples of how this approach has provided us with some insight into neural processing of psychological stress, stress habituation and control of a major physiological stress response system, the hypothalamic-pituitary-adrenal (HPA) axis.

Dr. Ron Tjalkens Assistant Professor; Department of Environmental and Radiological Health Sciences, Colorado State University

Title: "Glial-neuronal interactions in parkinsonism"

Abstract: Astrocytes are the principal non-neuronal cell type of the central nervous system and maintain neuronal homeostasis through provision of metabolic intermediates for ATP synthesis, modulation of neurotransmitter uptake, and protection against oxidative stress through the release of antioxidants. Additionally, it has been recently discovered that astrocytes coordinate synaptic transmission through intercellular networks that rely of release of “gliotransmitters” including ATP. This phenomenon of “gliotransmission” is critical to modulating synaptic activity and protecting against excessive excitatory neurotransmission. However, during conditions of stress and injury, astroglial trophic function is impaired and astrocytes can acquire a reactive phenotype characterized by increased production of inflammatory cytokines and nitric oxide (NO) that damages adjacent neurons and contributes to the progression of injury in neurodegenerative disorders such as Parkinson’s disease. Inducible expression of NOS2 is principally regulated by the transcription factor, nuclear factor kappa B (NF- ?ß), that is activated by multiple upstream signaling events, such as phosphorylation cascades, plasma membrane receptors, and oxygen radicals. The molecular regulation of such inflammatory genes and the impact of inflammatory activation of astrocytes on glial-neuronal homeostasis is the subject of studies in our laboratory.

Dr. Maggie Wierman, Professor, Department of Physiology and Biophysics, University of Colorado School of Medicine

Title: "Gonadotropin releasing hormone (GnRH) neuronal migration: role of tyrosine kinase receptor and G-protein coupled receptor signaling"

Abstract:Gonadotropin releasing hormone (GnRH) neurons are hypothalamic neurons that control reproductive competence. These neurons are unique in that they must migrate from the olfactory region into the forebrain to make appropriate connections to the anterior pituitary to activate gonadotropin production and eventuate in sexual maturation. Failure of migration of these neurons results in failure of puberty in animal models and in humans. We are studying the factors involved in GnRH neuronal migration. This seminar will discuss the tyrosine kinases (ex Axl family) and GPRS (ex chemokine receptors) and how they signal as potential candidates in this process. Understanding GnRH neuronal migration may give clues to other types of neuronal migration and also new targets for therapeutics to turn on or turn off the reproductive axis.

Dr. Ahmad Hariri, Assistant Professor, Department of Psychiatry, University of Pittsburgh School of Medicine

Title: “Imaging Genetics: Exploring the interplay of Genes, Brain & Behavior”

Abstract: Since the mid-20th century, ever-increasing attention has been given to identifying specific biological pathways that contribute to complex cognitive and emotional behaviors, an endeavor paramount to our understanding of how individual differences in these behaviors emerge and how such differences may confer vulnerability to psychiatric disease. Recent advances in both molecular genetics and noninvasive functional neuroimaging have begun to provide the tools necessary to explore these and other behaviorally relevant biological mechanisms. In this talk, I will outline an experimental strategy by which genetic effects on brain function can be explored using multimodal neuroimaging techniques. Specifically, I will use functional MRI and PET studies of genetically driven variation in serotonergic function on corticolimbic neural circuitry to highlight the effectiveness of this strategy to delineate biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness.