The
Laboratory on Behavioral Neuroscience investigates the behavioral actions of
brain neurotransmitters, using rodent models of symptoms of neuropsychiatric
diseases. Approaches include behavioral
neuropharmacology and behavioral genetics
Galanin is a neuropeptide that exerts inhibitory
modulation on acetylcholine and glutamate pathways relevant to learning and
memory. In the ventral hippocampus, we found that galanin induces delay-dependent
working memory deficits on T-maze
delayed alternation and operant delayed nonmatching to position, prevents
selective quadrant search in the Morris water task, and inhibits acetylcholine
release from the septohippocampal pathway. Galanin is overexpressed in the basal forebrain in Alzheimer�s disease,
while other neurotransmitters are declining, suggesting a unique role for
galanin in this disease. We are now
evaluating galanin receptor antagonists in learning and memory paradigms, to
test the hypothesis that blocking endogenous galanin may help alleviate the memory
deficits characteristic of Alzheimer�s disease.
Transgenic
and knockout mice, with mutations in genes expressed in the brain, provide powerful new tools for
understanding the genetic substrates of behavior. Using a wide variety of relevant behavioral paradigms, our
laboratory developed a three-tiered strategy for behavioral phenotyping that is
becoming widely used. Several
fascinating new transgenics and knockouts are presently being phenotyped,
including galanin overexpressing transgenic mice, a mouse model of Tay Sachs
disease, and knockouts for neurotransmitters receptors and transporters. Behavioral
genetics is further being pursued with quantitative trait loci linkage analyses of
mouse behavioral traits
relevant to schizophrenia and to anxiety.
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