Spring 2002 Seminar Series in Neuroscience

Tuesday Jan 22, 4-5 pm Dr. Nancy Zahniser, Department of Pharmacology and Neuroscience Program, HSC Regulation of the Dopamine Transporter: Drugs, Substrates, Presynaptic Receptors and Signaling Systems Abstract: The dopamine transporter (DAT) is crucial for limiting dopaminergic neurotransmission in the brain. About 10 years ago it came as somewhat of a surprise to realize that DAT activity and expression could be regulated not only by chronic administration of drugs, but also in a more dynamic manner response to acute stimuli such as substrates, presynaptic receptors and signaling systems. My talk will focus on studies from my lab that have provided support for these different types of DAT regulation. Our studies have utilized a wide variety of systems from Xenopus oocytes expressing human DAT to freely-behaving rodents. Tuesday Feb 5, 4-5 pm Alcino Silva, Departments of Neurobiology and Psychology, Brain Research Institute UCLA Molecular and cellular mechanisms of cognitive function and dysfunction Abstract: Our laboratory is studying the biology of learning and memory. We are interested in the molecular, cellular and circuit processes that underlie the storage and recall of information. To accomplish this we are using a variety of techniques including biochemistry, transgenic manipulations, pharmacology, in vitro and in vivo electrophysiology, neuroanatomical lesions and behavioral analysis. The focus of our studies has been on hippocampal dependent learning and memory. Our results implicate a variety of hippocampal mechanisms in learning and memory, including long term potentiation, short-term plasticity, the slow afterhyperpolarization and synaptic inhibition. We have found mutations that affect the induction of long-term changes in synaptic function and learning, and others that affect the stability of these synaptic changes and memory (but not learning). For example, our studies have demonstrated that the transcription factor cAMP responsive element binding protein (CREB) is critical for the consolidation and reconsolidation of long-term memory. Our laboratory is also interested in applying these findings to the development of treatments for learning and memory disorders, such as those observed with aging and in neurofibromatosis type I (NF1). For more information go to www.silvalab.com Tuesday Feb 19, 4-5 pm Richard Olson, Dept. of Psychology and Institute of Behavioral Genetics Genes & Environment in Reading Development Abstract: This talk will review behavioral and molecular-genetic research on the genetic and environmental etiology of dyslexia and related language disorders. Studies with identical and fraternal twins have revealed strong genetic influences on reading disabilities that are shared with disabilities in the awareness of and manipulation of abstract units of speech called phonemes. The deficit in phoneme awareness is most closely linked with the ability to phonologically decode (i.e., "sound out") new words and nonwords following the most common rules of English orthography. Another important skill in reading printed English words is the ability to recognize and remember the subtle differences in spellings for words that sound the same (bear, bare). Deficits in this ability have independent genetic influences as well as genetic influences that are shared with phonological reading and language deficits. The molecular genetic research is still in its early stages, but there have been replicated findings of linkage to a gene or genes in regions on chromosomes 6 and 18 for several reading-related phenotypes. Tuesday March 5, 4-5 pm Jonathan Cohen, Department of Psychology and Center for the Study of Brain, Mind, and Behavior, Princeton University Neural Bases of Cognitive Control: Computational Modeling and Neuroimaging Studies Abstract: Cognitive control is the ability to guide attention, thought and action in accord with internally maintained goals or intentions. Several decades of cognitive and neuroscientific research have focused on the mechanisms by which control influences processing (e.g., attentional effects in sensory processing, goal directed sequencing of motor output, etc.), and disturbances of these mechanisms in psychiatric disorders such as schizophrenia and depression. While much has been learned, a major gap in our understanding concerns the mechanisms that determine how control is allocated. This presentation will provide an overview of recent work drawing upon neural network modeling, fMRI and ERP recordings to understand these mechanisms. Models will be presented of specific component processes and their proposed neural implementation, including the maintenance and updating of control representations (prefrontal cortex and dopaminergic neuromodulation) and their influence on task processing, performance monitoring (anterior cingulate cortex), and the feedback influence of monitoring on the modulation of control state (locus coeruleus). In addition to providing new insights into the mechanisms underlying cognitive control, this work highlights the value of the combined use of neural network modeling and measurements of brain function in efforts to identify and understand the neural bases of cognitive processes. Tuesday March 19, 4-5 pm Andrew Miller, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine When Not Enough is Too Much: The Glucocorticoid Deficiency Hypothesis of Stress Related Disorders Abstract: Although previous theories have emphasized the pathological potential of hypercortisolism in stress-related disorders, more recent data suggests that deficient glucocorticoid signaling may have equally devastating effects on bodily function, related in part to the role of glucocorticoids in restraining immune activation and inflammation. Neuroendocrine and immune data support the hypothesis of glucocorticoid deficiency in a variety of stress-related disorders. Consequent immune activation may contribute to the pathologies of these conditions including behavioral symptoms such as depression, fatigue and pain as well as cell loss in the central nervous system, decreased bone metabolism, insulin resistance and impaired acquired immune responses. From an evolutionary perspective, glucocorticoid deficiency may serve an adaptive purpose by biasing the immune system during chronic stress toward more aggressive early, innate immune responses and possibly mood elevation. Finally, this paradigm shift from an emphasis on glucocorticoid excess to glucocorticoid deficiency has treatment implications regarding relevant therapeutic strategies involving enhancement of glucocorticoid signaling pathways, in particular glucocorticoid receptor function. Tuesday April 9, 4-5 pm Dr. Diego Restrepo, Neuroscience Program, Rocky Mountain Taste and Smell Center, Department of Cellular and Structural Biology HSC How the Nose Knows: Emerging Principles for Natural Odor Representation in the Brain Abstract: The olfactory system detects small differences in the composition of natural odorants, made up of hundreds of molecules. Odorous quality is hypothetically represented by a combinatorial code - activation of distinct, but overlapping subsets of olfactory receptors resulting in activation of a distinct subset of glomeruli in the olfactory bulb. Here we show that modification of a single gene (the K gene of the major histocompatibility locus), which results in a subtle change in the odiferous quality of urine, causes a small, but significant change in the glomerular activation pattern. Moreover, the magnitude of disparity between urine-evoked glomerular activation patterns is predictive of the extent of genetic difference among the donors and the receiver's ability to discriminate. These data show that the combinatorial code applies to natural odors. Tuesday April 23, 4-5 pm Allan Collins, Institute of Behavioral Genetics & Psychology, University of Colorado at Boulder Genetic Approaches Reveal Functions of Neuronal Nicotinic Receptors Abstract: Epidemiological studies have repeatedly demonstrated that alcoholics are almost invariably smokers, generally very heavy smokers. King James II commented on this relationship in 1620 when he noted that the worst smokers were the drunken sots. One of the major goals of our research team has been to attempt to explain the booze-butts relationship. Given that common genes seem to influence alcoholism and smoking in humans, we have used genetic and neurochemical strategies in an attempt to identify common actions of alcohol and nicotine. The results of recent experiments which used classical genetic strategies and null mutant/gene knockin approaches to establish roles for specific neuronal nicotinic receptor subtypes in modulating behavioral responses to nicotine and ethanol will be discussed. As we go along, data will be presented which show how gene knockout mice can be used to answer questions that range from what is the composition of naturally-occurring neuronal nicotinic receptors to what role do these receptors play in regulating "normal" as well as drug-induced behaviors?