Fall 2005 Seminar Series in Neuroscience

Dr. Danny Winder Department of Molecular Physiology and Biophysics Vanderbilt University, Nashville, TN

Title:"Synaptic Modulation in the Bed Nucleus of the Stria Terminalis and its Role in Anxiety
and Addiction"

Abstract: Drug addiction is often described as a chronically relapsing disorder. Stress and anxiety are the most common reasons cited by addicts for relapse behavior. Through the use of animal models, a neural circuit has been described that contributes to aspects of this stress-induced relapse behavior. In particular, a region known as the bed nucleus of the stria terminalis (BNST) has been heavily implicated. Anatomical data are consistent with a role for this region in integrating stress and reward interactions, as the region receives inputs conveying information on multiple modalities of stressors, and then projects both directly to the hypothalamus to control recruitment of the autonomic nervous system, as well as directly into the reward system through interconnections with the ventral tegmental area and the nucleus accumbens. We are currently utilizing a combination of acute brain slice and behavioral paradigms in mouse models to attempt to determine synaptic and molecular mechanisms contributing to the roles the BNST plays in animal behavior.

Dr. Wilma Friedman, Department of Biological Sciences
Rutgers University, Newark, NJ

Title: "Nerve growth factor in the brain:
A double-edged sword"

Abstract: Neurotrophic factors are proteins that influence survival and function of neurons in the central and peripheral nervous systems. Recent studies, however, have shown that specific neurotrophic factors may cause neuronal death instead of survival, depending upon which receptors and signaling pathways are activated. We are examining mechanisms governing death- vs. survival-promoting actions of nerve growth factor and related neurotrophins during development and under inflammatory conditions.

Dr. David Sweatt Department of Neuroscience, Baylor College of Medicine, Houston, TX

Title: "Signal Transduction 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. Frank Moore Distinguished Professor of Zoology, Oregon State University, Corvallis, OR

Title: "How Hormones Control Behaviors:
Stress, Sex, and Drugs in an Amphibian"

Abstract: Frank Moore’s research uses an amphibian model to investigate the neuroendocrine control of reproductive behaviors. This model has provided some new insights into the hormonal mechanisms that underlie short-term changes in behavioral state, focusing mainly on what, where, and how questions about hormones that turn-on and turn-off male sexual behaviors. This seminar will focus on how vasotocin (Ile3-vasopressin) and corticosterone (a dominant stress hormone) interact at the molecular, neurophysiological, and behavioral levels to turn-on and turn-off male sexual behaviors.

Dr. Celia Sladek, Department of Physiology & Biophysics, UCHSC, Aurora, CO

Title: “Cardiovascular Regulation of Vasopressin Secretion: Impact of co-released neurotransmitters and unique signaling cascades”

Abstract: A decrease in blood volume or blood pressure is a potent stimulus for vasopressin release from the posterior pituitary. This information is transmitted to the vasopressin neurons via a multisynaptic pathway with the A1 catecholamine neurons of the brainstem providing the final link. The A1 neurons express several neurotransmitters and neuropeptides including norepinephrine, ATP, neuropeptide Y, and substance P. In studies designed to evaluate the significance of this multiple transmitter system, we observed prominent potentiation of vasopressin release by co-administration of these agents (J. Neurosci. 20: 8868-8875, 2000; Am. J. Physiol. 280:R69-R78, 2001). These observations precipitated studies to: 1) understand the cellular mechanisms underlying the potentiated responses and 2) identify the physiological importance of these interactions. Use of live cell imaging techniques for monitoring intracellular calcium and confocal microscopy to study receptor trafficking has provided provocative evidence for activation of unique signaling cascades. Since neurotransmitters and neuropeptides are co-released at many (perhaps all) synapses, these studies have broad implications for the CNS.

Dr. Natalie Ahn, Department of Chemistry & Biochemistry and HHMI, UC-Boulder

Title: "Applications of proteomics to signal transduction"

Abstract:The field of proteomics has enjoyed rapid growth in recent years, driven by new technologies and applications involving mass spectrometry. I will discuss strategies using proteomics to analyze cellular responses as well as protein-protein interactions, and how we are applying these methods to investigate signaling mechanisms. (1) By combining 2D gels and mass spectrometry with molecular pharmacological approaches, we successfully identified novel targets for Rho GTPase pathways, including a previously uncharacterized gene which appears to function in cancer cell invasion and phosphorylation of proteins involved in cell adhesion. (2) An alternative strategy for protein profiling, variously referred to as MudPIT, multidimensional LC/MS/MS, or "bottom up" shotgun proteomics, involves solution proteolysis of a complex mixture of proteins, followed by multidimensional chromatographic separation of peptides prior to LC-MS/MS sequencing. (3) Hydrogen exchange mass spectrometry (HX-MS) is a method that can be used to probe protein-protein interactions and protein conformational mobility. I will present applications of this method to investigate substrate-enzyme interactions in MAP kinases.