Project Summary

Hui Zhang, Ph.D. (Young Investigator 2005) of Columbia University, proposes studying neurotransmission in a mouse missing a schizophrenia susceptibility gene called AKT1. Recent studies have shown that mice missing the AKT1 gene exhibited greater sensitivity to sensorimotor gating disruption by dopamine releasers, such as amphetamines. But no study has been done to investigate how the absence of the gene affects synaptic transmission and plasticity, which is critical for understanding mechanisms of abnormal behaviors. In this proposal, Dr. Zhang will examine both dopaminergic and glutamatergic transmission, the two major pathways thought to be dysregulated in schizophrenia, in AKT1 knockout mice using optical, electrophysiological and electrochemical recordings. Dr. Zhang will further investigate how these two pathways are affected under amphetamine challenge in the knockout mice and their wild-type littermates. These experiments will thus help to identify abnormal synaptic transmission that may occur in schizophrenia and possibly suggest novel pharmacological interventions.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

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