Fall 2001 Seminar Series in Neuroscience

Tuesday Sept 11, 4-5 pm Dr. Catherine Wooley, Department of Neurobiology and Physiology, Northwestern University Effects of Estrogen on Hippocampal Circuitry Abstract: How do ovarian steroid hormones like estrogen affect the brain? Answering this question is a focus of research in my lab. Specifically, we study how fluctuating levels of estradiol regulate structure and function of hippocampal circuitry. The hippocampus is a brain region that normally plays an important role in cognitive and sensory information processing and, under pathological conditions, is a circuit that can generate and propagate seizure activity. Our research uses a multidisciplinary approach that combines light and electron microscopy, electrophysiological recording from hippocampal slices and behavioral testing to understand the 'hows' and 'whys' of steroid hormone regulation of synaptic connectivity within the hippocampus. Tuesday Sept 25, 4-5 pm Dr. Barry E. Stein, Department of Neurobiology & Anatomy, Bowman Gray School of Medicine,Wake Forest Univ. Merging of the Senses: How the Brain Creates Multisensory Integration Abstract: One of the brain's critical roles is the detection and identification of external events. The neural processes underlying this capability determine how we perceive our world and the behaviors we must plan in a given circumstance. Since survival depends on the accuracy and speed of these processes, it is not surprising to find that they have been powerful driving forces in evolution and have led to the complex array of specialized sensory systems that characterize all higher organisms. The perceptual consequences of integrating the information received from these different sensory channels, and in constructing a unified percept of the world, have intrigued philosophers of science since the time of ancient Greece. Indeed both Democritus and Aristotle had mused about these issues. The psychological literature has become rich in examples of compelling cross-modal illusions that result from minor disruptions in this process. Indeed, one of these (the "McGurk Effect") is used extensively to demonstrate the importance of visual-auditory integration in normal speech perception. Although we are generally unaware of the underlying process, "multisensory integration" results in a profound enhancement in the detection of, and speed of reaction to, a host of external events. The neural mechanisms underlying these processes have remained elusive for some time. However, the recent use of the multisensory neuron in a midbrain structure as a model, has provided some insight into the neural principles that underlie the synthesis of cross-modal cues. Though species-specific distinctions in the stimuli involved reflect adaptations to different ecological circumstances, the cross-species similarities in these governing principles suggest a remarkable conservation in this fundamental capability throughout vertebrate evolution. How these neural processes operate, how they are adapted to context, why they take so long to develop during early ontogeny, and how they relate to overt attentive and orientation behavior will be discussed in detail. Tuesday Oct 9, 4-5 pm Dr. Don Finan, Dept. of Speech, Language and Hearing Sciences, University of Colorado at Boulder Central Pattern Generation and Complex Behaviors: A Role for Speech Production? Abstract: At birth, the human infant has only one task: to survive. Luckily, the infant is endowed with complex networks of neurons whose responsibilities lie in generating feeding and respiratory behaviors. The neural systems responsible for the generation of these (and other) rhythmic behaviors are often termed "Central Pattern Generators" (CPGs). Traditionally, CPGs were considered to be inflexible units whose output was stereotypical and well-defined. Recent experiments in a number of animal species, however, have shown that that motor behavior evolves from dynamic changes that take place at the molecular, cellular, and network level. There are a variety of sensorimotor processes that either drive or provide evidence of this dynamic elaboration in structure and function of central nervous networks capable of patterned output. Sensorimotor entrainment is one such phenomenon that has been explored in the human infant as well as in many other animal models. Several experiments have demonstrated that CPGs can be modified (entrained) through endogenous and external loads. Results of these and similar experiments have resulted in an expansion of the CPG concept to reflect the capacity for dynamic adaptation. The roles that CPGs may play in the development and production of speech will be discussed. Tuesday Oct 23, 4-5 pm Dr. Robert Handa, Dept. of Anatomy & Neurobiology, Colorado State University Functional variants of estrogen receptor beta in the brain: roles in development and the hormonal responses to stress. Abstract: The cloning of a second form of estrogen receptor in 1996 (termed estrogen receptor beta) has provided new insights into the mechanisms by which estrogen might impact neural function. Mapping the expression of ERbeta in brain has demonstrated a unique distribution which only partially overlaps that of the classical ER alpha. In particular, co-localization studies show that very high levels of ERbeta are found in neuroendocrine neurons of the paraventricular and supraoptic nuclei, potentially indicating their involvement in the regulation of hormone secretion. Careful examination of ERbeta mRNA in brain has demonstrated that several splice variants exist. The wild-type form of receptor has been termed ER-?1. An in frame insertion between exons 5 and 6 has been termed ER-?2, whereas deletions of exon 3 or exon 4 have been termed delta-3 and delta-4, respectively. Our studies have determined that each of these variants are expressed in a region and developmental specific pattern. The delta-4 variant is expressed at highest levels in the adult hippocampus, whereas the beta-2 variant is expressed at high levels in the developing hypothalamus and hippocampus. Next to ER beta-1, the delta-3 variant is the most abundant form in the adult hypothalamus. Our studies using transient transfection techniques have also demonstrated that each of these variants exhibit unique properties of transcriptional regulation and nuclear trafficking different from that of ER alpha or ER beta1. Furthermore, interactions between estrogen receptors, their variants, and glucocorticoid receptors in the regulation of gene expression has been demonstrated using endogenous neuropeptide promoters. Such studies provide further insight into the diversity of estrogen action in the developing and adult brain, particularly in regard to non-reproductive functions. Tuesday Nov. 6, 4-5 pm Dr. Joe Falke, Dept of Chemistry & Biochemistry, University of Colorado at Boulder The Conserved C2 Domain: Calcium Trigger for Neurotransmitter Release and Other Membrane Signals Abstract: The C2 domain is a conserved signaling motif widely found in signaling proteins that regulate membrane signaling events in response to cytoplasmic calcium fluxes. For example, the synaptic vesicle protein synaptotagmin I contains a C2 domain believed to be the calcium-activated trigger that initiates synaptic vesicle fusion and neurotransmitter release. The Falke laboratory is currently comparing the activation parameters and molecular mechanisms of C2 domains from synaptotagmin I and other important signaling proteins. The seminar will illustrate how these comparative studies are revealing the features of the C2 domain which are specialized for synaptic signaling and other cellular functions. Week of November 10-15. No Seminar. Society for Neuroscience meeting. Tuesday Nov 27, 4-5 pm Dr. Steven F. Maier, Department of Psychology and Director of the Center for Neuroscience, University of Colorado at Boulder Stressor Controllability, Anxiety, and Serotonin Abstract: The degree of behavioral control that an organism (rat to human) has over a stressor is one of the most potent factors that determine the behavioral and physiological impact of the stressor. Stressors over which the organism has no control produce a constellation of changes that are very close to what is meant by "anxiety". This talk will review our work directed at understanding the neural mechanisms which mediate these changes, and perhaps anxiety more generally. Focus will be on a) alterations within serotonergic neurons located in the dorsal raphe nucleus as the proximate cause of the behavioral changes induced by uncontrollable stressors b) the neurochemical mechanisms responsible for these change, and c) forebrain inputs to the DRN that process stressor controllability information and drive its activity. Implications of this circuitry for understanding both anxiety and drug addiction will be discussed. Tuesday Dec 11, 4-5 pm Dr. Heidi Day, Dept. of Psychology, University of Colorado at Boulder Stress and the Central Extended Amygdala Abstract: There is substantial evidence to support the idea that the central nucleus of the amygdala (CEA) is important for the elicitation and integration of behavioral, autonomic and possibly emotional responses to fear, anxiety and stress. Many groups have been involved in determining the neural circuitry underlying different types of stress and to this end, have looked at the stress-induced expression of immediate early genes within the brain, in particular, c-fos mRNA or its protein product Fos. C-fos mRNA and Fos protein have been shown to be robustly expressed in the CEA and a closely related structure, the oval subnucleus of the stria terminalis (BSTov), by a number of systemic stimuli that are considered stressful, such as peripheral injections of cholecystokinin, interleukin-1œ or amphetamine. However, somewhat surprisingly, stressors that are considered to be more psychological in nature, such as fear conditioning, restraint, forced swim, foot-shock, audiogenic stress, open-field or novelty, generally induce relatively low levels of c-fos mRNA or Fos protein in the CEA. However, we have recently shown that novelty inhibits amphetamine-induced c fos mRNA expression in the CEA and BSTov. This raises the possibility that psychological stress may in fact actively inhibit neurons of the CEA and BSTov. Given that the vast majority of the neurons in these regions are themselves inhibitory, their inhibition would have important implications for the neural circuitry involved in responses to psychological stress.