Fall 2003 Seminar Series in Neuroscience

Dr. Harald Sontheimer, Dept. Neurobiology, Univ. Alabama

Title: Chloride channels and amino acid transporters contribute to the growth and invasion of primary brain tumors

Abstract: Primary brain tumors, glioma, are amongst the most deadly cancers known. They exhibit a unique biology characterized by significant destruction of peritumoral brain tissue and diffuse invasion into the healthy brain. Recent studies by us and others have demonstrated that glioma cells co-opt ion channels and amino acid transporters to accomplish these tasks. Specifically, Cl- ion channels allow for the dramatic cell shrinkage required for cells to migrate through the tortous extracellular brain spaces, while amino-acid transporters mediate the release of glutamate which causes excitotoxic tissue destruction.

Dr. Sue Moenter, Division of Endocrinology & Metabolism, University of Virginia Health Sciences, Dept of Medicine

Title: GABAergic regulation of gonadotropin-releasing hormone neurons

Abstract: Reproduction is not necessary for the survival of the individual, and is thus tightly regulated by the central nervous system via a variety of cues from both the external environment (e.g., food availability, photoperiod) and the internal environment (e.g., gonadal steroid feedback, stress). The gonadotropin-releasing hormone (GnRH) neuron is the final point for integrating this information, and the pattern of hormone release from these cells determines if an individual is fertile or not. Reproduction is fairly simple to study in the whole animal, so we know a lot about conditions that favor GnRH release and those that inhibit it. Over many years, this knowledge was combined with knowledge of the actions of neurotransmitters elsewhere in the brain to generate hypotheses about the neurobiological mechanisms that brought about changes in GnRH release. One of the most prevailing of these postulates is that GABA, which is the dominant inhibitory neurotransmitter in the central nervous system, inhibited GnRH neurons. Our ability to study GnRH neurons directly has called this dogma into question. In this talk, I'll present both the biophysical studies that lead us to challenge the prevailing view, and corroborating physiological evidence on the action of GABA on GnRH neurons from animals in various reproductive states.

Dr. Carla Shatz - Chair, Dept of Neurobiology, Harvard Medical School

Title: Connections in the adult CNS are highly precise.

Abstract: In the visual system, retinal ganglion cells connect to target LGN neurons in adjacent, non-overlapping eye-specific layers. During development, retinal inputs are intermixed and the layers emerge as axons from the two eyes remodel. Remodeling requires ganglion cell action potentials, which are endogenously generated in utero long before rods and cones are present: ganglion cells fire spontaneously and synchronously, generating "waves" of activity that sweep across retinal domains. Waves are also required for regulation of gene expression by LGN neurons, including -surprisingly-Class I major histocompatibility complex (MHC I). In mice lacking cell surface class I MHC, or CD3 zeta, development of the retinogeniculate projection is abnormal and adult mice have supranormal hippocampal LTP and lack LTD. Thus, these molecules are required for normal activity-dependent structural and functional synaptic modifications. These observations indicate that long before visual experience, nerve cell function is essential for activity-dependent gene expression and for the initial structural remodeling that leads ultimately to the adult precision of connectivity.

Dr. Jim Herman, Dept. of Psychiatry, University of Cincinnati

Title: Hierarchical Neurocircuits Regulating the Stress Response

Abstract: Glucocorticoid stress responses are vital for health and survival of all vertebrate organisms. In general, these responses redirect bodily resources to deal with real or perceived homeostatic disturbances. Thus, while it is of paramount importance to mount appropriate responses, it is also essential to assure that these responses are short-lived. Accordingly, the consequences of glucocorticoid dysregulation are dire, and range from frank somatic disease (e.g., type II diabetes) to affective dysfunction (depression, PTSD) to neurodegenerative processes and age-related cognitive decline. Our group is particularly concerned with understanding how the brain exercises such exquisite control of hormonal stress responses, and what happens when this control goes awry. On the basis of prior work in our laboratory and others, we have developed a dual-process theory of stress integration, with circuits compartmentalized into those governing brain-generated responses (limbic system) and those controlling frank homeostatic challenge (brainstem). Naturally, as we have delved into the workings of these systems, we find that our nice neat hypothesis does not quite fit with our newest findings. In this talk I will present the data that refutes our prior hypothesis, and discuss a new hypothesis-in-progress to encompass our novel and exciting data.

Dr. Mani Ramaswami , Department of Molecular & Cell Biology & Division of Neurobiology, Arizona Research Labs, University of Arizona, Tucson

Title: Molecular mechanisms of long-term memory; can cancer biology inform experimental psychology?

Abstract: Classical experiments in human psychology predicted two mechanistically distinct forms of memory: short-term accessed by cramming, and long-term accessed by multiple episodes of spaced practise. More modern studies on model organisms have confirmed mechanistic differences between these forms of memory. Genetic and molecular analyses have revealed synaptic signaling pathways that transduce specific forms of neural activity into transient or persistent synaptic change. Using evidence largely from work in Drosophila, I will discuss how synaptic activity may be interpreted by cells to trigger lasting synaptic changes that likely underlie long-term memory. I will suggest that fine aspects of synaptic signaling which determine the duration of plasticity may be similar to signaling processes identified and studied by cancer biologists. In conclusion, the potential for molecular explanations for psychological phenomena will be discussed.

Dr. Christine Yoshinaga-Itano, Dept of Speech, Language & Hearing Studies, University of Colorado at Boulder

Title: Sensitive Periods in the development of deaf and hard-of-hearing infants and toddlers

Abstract: The study of children with congenital hearing loss can provide evidence of sensitive periods of language development. Research on the communication development of Colorado children with significant hearing loss shows evidence of a sensitive period in the first six months of life for identification of hearing loss and initiation of intervention. Early identification of hearing loss in the first six months of life coupled with initiation of intervention results in age-appropriate language development as compared to language development that is 50-60% of the rate of normal language development for later-identified children (after 6 months of age). Theoretical discussions regarding why the evidence for this sensitive period is so robust in the data have centered around whether the outcomes are a result of a sensitive period for the development of auditory perception or language. Subsequent data analysis indicates that the sensitive period for auditory perception has a longer timeline than for semantic language development, perhaps through the first five years of life. Semantic language development of the children with congenital hearing loss has been particularly resistant to change once significant delays in development occur in the first year of life. Because these developmental data indicate the significance of access to a competent language system within the first year of life, a quest to determine whether studies of neurological reorganization could help to explain the nature of these changes has become a new challenge for our field of study. Particularly interesting has been the study of children who derive little or no benefit from conventional amplification but after cochlear implantation surgery these children evidence a rapid transition from a visual/motor language system (sign language) to a competent spoken English system. This transition occurs within 12-14 months post cochlear implantation surgery, with the first 6 months devoted to learning the individual sounds of spoken English and the second 6 - 8 months transferring that knowledge of almost 600 signed vocabulary words to intelligible spoken speech. This documentation has been found only in cases when the child's sign language ability is at age level prior to cochlear implantation and predominantly when surgery occurs prior to two years of age. Presumably these children had not begun to develop an auditory neural pathway until the cochlear implantation. Neurological studies for these children are particularly challenging since the magnet which is surgically placed in the child's head results in inability to use MRI. 

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