Spring 2003 Seminar Series in Neuroscience

Tuesday Feb 4, 4-5 pm Christopher Link, Institute for Behavioral Genetics, University of Colorado at Boulder

TITLE: Transgenic modeling of neurodegenerative diseases


Abstract: My lab has engineered the well-studied nematode worm Caenorhabditis elegans to express human proteins involved in neurodegenerative diseases, with hopes of using the experimental tools available in C. elegans to understand the molecular/cellular basis of these diseases. To date most of our work has been with transgenic worms engineered to express the human beta amyloid peptide, which is generally believed to be central to Alzheimer's disease pathology. In my talk, I will described how we have used this model system to investigate 1) the relationship between beta amyloid peptide sequence, amyloid formation, and toxicity, 2) the role of chaperone proteins in the intracellular metabolism of the beta amyloid, and 3) the global transcriptional response to beta amylod peptide expression, as assayed by DNA microarray analysis. I will also talk a little about how we are extending this approach to other neurodegenerative diseases associated with aggregating proteins (e.g., Huntington's, ALS, Parkinson's, etc).
Tuesday Feb 18, 4-5 pm Mike Mauk, Department of Neurobiology and Anatomy, Univ of Texas Medical School

TITLE: Trying to understand the cerebellum well enough to build one

Abstract: Since brain systems process information -- they convert inputs to output according to rules established by their synaptic organization and physiology -- we aspire to understand the cerebellum at this level. Our approach has been to combine empirical studies of Pavlovian eyelid conditioning with computer simulations of the cerebellum. I will describe:
1) how eyelid conditioning lends itself to the study and simulation of the cerebellum,
2) a commitment to simulations where correct behavior is not built in, and thus where both failures and successes can be informative, and
3) recent experiments testing mechanistic predictions from the simulation.
Tuesday Mar 4, 4-5 pm Glen Martin, Dept. Otolaryngology, UCHSC

TITLE: Phenotyping hearing in mice with otoacoustic emissions.

Abstract: Hearing loss affects more than 25 million Americans and costs over 50 billion dollars each year. Inherited deafness affects one child in every 2000. In hereditary deafness, the bulk of sensorineural hearing losses are of outer hair cell origin. Otoacoustic emissions are based upon the responses of the outer hair cells (OHCs) of the cochlea. Because many hearing defects are nonsyndromic, an efficient screen, based upon distortion-product otoacoustic emissions (DPOAEs) for hearing defects in mice, would greatly facilitate the search for deafness genes. We have developed an effective screen for hearing loss in mice using DPOAEs and have tested over 24 strains determined to have normal hearing with auditory brainstem evoked-response techniques. We have also begun to screen mice for susceptibility to noise exposure and have found that the MOLF/Ei strain has excellent hearing and exceptional resistance to noise. This work is part of our laboratory’s interest in understanding the basis of the well-documented variability in susceptibility and resistance to noise in humans.
Tuesday March 18, 4-5 pm

John Gabrieli, Department of Psychology, Stanford

TITLE: "Emotion and Memory Systems of the Human Brain

Abstract: The limbic system includes structures associated with both memory and emotion, and the amygdala in particular has been characterized as a crossroads of memory and emotion. I will review recent findings from our research that characterize amygdala processing via functional magnetic resonance imaging (fMRI). These studies demonstrate both automatic and controlled aspects of amygdala function, and variation of amygdala function due to sex, personality, and age.

Tuesday April 8, 4-5 pm Monika Fleshner, Dept of Kinesiology & Applied Physiology, University of Colorado at Boulder

TITLE: Exercise prevents learned helplessness: The role of 5HT

Abstract: Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) are implicated in mediating learned helplessness (LH). DRN 5-HT neurons are hyperactive during uncontrollable stress, resulting in desensitization of 5-HT type 1a (5-HT1a) inhibitory autoreceptors in the DRN. 5-HT1a autoreceptor down-regulation is thought to induce transient sensitization of DRN 5-HT neurons, resulting in excessive 5-HT activity in brain areas that control the expression of learned helplessness behaviors. Exercise has antidepressant / anxiolytic properties and results in dramatic alterations in physiological stress responses, but the neurochemical mediators of these effects are unknown. Based on the results of our current studies, we suggest that exercise reduces LH by blunting stress induced activity of DRN 5-HT neurons, and increasing basal expression of DRN 5-HT1a autoreceptor mRNA. An increase in 5-HT1a inhibitory autoreceptor expression may contribute to the attenuation of DRN 5-HT activity and the prevention of LH in physically active rats.
Tuesday April 22, 4-5 pm Roger Traub, Dept of Physiology and Pharmacology, SUNY Health Science Center

TITLE: Contrasting roles of axonal (pyramidal cell) and dendritic (interneuron) electrical coupling in the generation of neuronal network oscillations

Abstract: Electrical coupling between pyramidal cell axons, and between interneuron dendrites, have both been described in the hippocampus. What are the functional roles of the two types of coupling? Interneuron gap junctions enhance synchrony of gamma oscillations (25-70 Hz), in isolated interneuron networks, and also in networks containing both interneurons and principal cells, as shown in mice with a knockout of the neuronal (primarily interneuronal) connexin36. We have recently shown that pharmacological gap junction blockade abolishes kainate-induced gamma oscillations in connexin36 knockout mice; without such gap junction blockade, gamma oscillations do occur in the knockout mice, albeit at reduced power compared to wild-type mice. As interneuronal dendritic electrical coupling is almost absent in the knockout mice, these pharmacological data indicate a role of axonal electrical coupling in generating the gamma oscillations. We could thus here construct a network model of an experimental gamma oscillation, known to be regulated by both types of electrical coupling. In our model, axonal electrical coupling is required for the gamma oscillation to occur at all; interneuron dendritic gap junctions exert a modulatory effect..