Fall 2002 Seminar Series in Neuroscience

Ed Dudek, Dept of Anatomy & Neurobiology, Colorado State Univ.

Neuronal injury, axonal sprouting and synaptic reorganization: a possible cellular mechanism for temporal lobe epilepsy
Abstract: Approximately two percent of the human population has epilepsy, a neurological disorder that is characterized by chronic seizures. Several forms of brain injury can lead to epilepsy, which may cause additional neurodegeneration and contribute to the progressive decline characteristic of some epilepsy syndromes. Temporal lobe epilepsy, in particular, is often devastating and medically intractable. This seminar will introduce the clinical problem of temporal lobe epilepsy, and will then outline a series of experiments that aim to test one hypothesis concerning a possible mechanism of temporal lobe epilepsy. The central hypothesis is that seizures and neuronal injury lead to axonal sprouting and the formation of new recurrent excitatory circuits, which contribute to epileptic seizures. A corollary to this hypothesis is that recurrent inhibitory circuits mask the recurrent excitatory circuits. Electrophysiological experiments on hippocampal slices from an animal model of temporal lobe epilepsy, the kainate-treated rat, have been conducted to test these hypotheses. An overview of our recent data concerning these hypotheses will be presented in this seminar, and will be discussed in relation to the controversies in this field. Several directions for future research will be outlined.

Barry Jacobs, Program in Neuroscience, Princeton Univ.

Serotonin & Depression: Two Perspectives

Abstract: My laboratory’s research has been focused on brain serotonin for the past 30 years. Recently, our neurophysiology work (single cell recordings in behaving animals) and our cell biology work (cell proliferation) have provided some interesting perspectives on human psychopathology.

Brenda Lonsbury-Martin, Department of Otolaryngology, University of Colorado Health Sciences Center

Insights into hearing processes using otoacoustic
emissions

Abstract: Twenty-five years have passed since it was discovered that the ear naturally produces soft sounds called otoacoustic emissions. Otoacoustic emissions result primarily from the receptor-potential induced microvibrations or the electromotility of outer hair cells, which are responsible for the remarkable attributes of hearing including sensitive thresholds, sharp frequency tuning, and precise timing. Because they so intricately depend on the healthiness of the outer hair cell system, which represents the receptor class that is most susceptible to cochlear insults, otoacoustic emissions make ideal measures for a number of fundamental and practical purposes concerning the auditory system. This lecture will relate how a laboratory that uses animal models to further our understanding of normal and pathological hearing has used otoacoustic emissions to constructively study cochlear function and dysfunction. Findings ranging from using emissions to track the development of noise- or drug-induced hearing loss to phenotyping ear function in inbred strains of mice, and understanding the contribution that various regions of the organ of Corti make to the processing of acoustic signals will be reviewed. Finally, the role that otoacoustic emissions play in furthering our understanding of cochlear efferent-system function will be addressed.

Chris Evans, Neuropsychiatric Institute, UCLA

An Opioid For Every Occasion

Abstract: The talk will review the status of opioid pharmacology with regard receptor structure and superstructure, as well as signaling pathways activated via opioid receptors both in the absence and in the presence of agonists. Trafficking of opioid receptors will then be addressed with a focus on the functional significance of differential agonist-induced trafficking and opioid desensitization/tolerance. Data showing areas of brain with activated MAPK following acute and chronic agonist and antagonist treatments will be presented and related to behavioral changes including reward and aversion. Finally, our recent evidence for ligand-directed signaling and the potential for agonist- selective activation of discrete signaling pathways will be discussed.

Michael Stowell, Dept of Molecular, Cellular & Developmental Biology, CU-Boulder

Pursuing the structural and architectural basis of synaptic transmission and plasticity

Abstract: Our research is focused on molecular and supramolecular structures that facilitate communication between neurons at the chemical synapse. We are particularly interested in the architectural arrangement of signaling molecules and enzymes, and characterizing the ways in which such molecular assemblies are formed and undergo changes during synaptic transmission and modulation. I will focus on two processes that occur at the chemical synapse and two proteins that are essential to these processes: dynamin and the acetylcholine receptor. We have investigated the structural changes that dynamin undergoes during its catalytic cycle and have proposed a model for dynamin's action. I will also discuss the structure and mechanism of the acetylcholine receptor (AChR). The AChR is the archetypal ligand gated ion channel and we have investigated two structural states of the AChR using cryo-electron microscopy and image reconstruction. The data provide the first structural evidence for a "two-gate" mechanism and help to understand a fundamental phenomenon of ligand gated ion channels.

Bill Greenough, Depts. Psychiatry and Cell and Structural Biology, Center for Advanced Study, Beckman Institute, Univ. Illinois-Urbanna/Champaign

Learning, Memory, Exercise and the Brain

Abstract: The brain stores information both in development and during adult learning, and increasing evidence suggests common mechanisms. Memory is broadly conceived for our purposes, including both traditional psychological forms of learning and memory, and forms of information that the nervous system may store of which we are not aware, such as the organizational effects of a neuromodulatory substance, of physical exercise, or of early sensory experience on the developing nervous system. We study brain mechanisms of information storage using multiple and integrated approaches ranging from work at the molecular and cellular levels to that of the behavior of whole animals. We have studied the integrated memory process as exhibited, for example, in rats exposed to a complex and changing housing environment and in rats required to learn complex motor skills. We have begun to study some of the events that underlie the formation of synaptic connections between neurons, the relationship of these events to phenomena induced behaviorally, and the role of cells other than neurons, such as glial cells. Finally, we are examining the links between behavior and gene expression in situations in which various forms of brain adaptation to the demands of the environment are taking place. Our recent research has begun to focus upon FMRP, the protein that is absent in fragile X syndrome, the leading genetic cause of mental retardation. This work has advanced our understanding both of the specific role of FMRP at the synapse and of the cellular changes that may stabilize newly formed synaptic connections. As a result, we are increasingly understanding the pathology of the largest known cause of inherited mental retardation as well as the mechanisms whereby experience may be recorded in brain structure.