Project Summary

Lee Zuckerman, Ph.D. (Young Investigator 2005) of Columbia University, proposes studying how alterations in the expression of certain dopamine receptors (D2R) in the striatum lead to prefrontal cortex hypofunction, two processes which are implicated in schizophrenia. Recently, Dr. Zuckerman developed a line of transgenic mice with an increased level of D2 receptors in the postsynaptic target neurons of the striatum. These mice exhibit specific deficits in working memory and behavioral flexibility tasks, which require the prefrontal cortex in rodents. The pathway via which the striatum may affect cortical dopamine function involves the ascending projections of midbrain ventral tegmental area (VTA) dopamine neurons to the striatum and the prefrontal cortex. By using extracellular single unit recording and stimulation techniques in anesthetized mice, Dr. Zuckerman proposes to study the mechanisms by which striatal D2 over-expression could lead to impairments in prefrontal cortex-dependant tasks. Results should allow a better understanding of the role of increased striatal dopamine transmission in frontal hypofuncion and the difficult-to-treat cognitive symptoms of schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

Search Again