Project Summary

Sebastien Thuault, Ph.D. (Young Investigator 2006) of Columbia University, will use a mouse model to study the prefrontal-cortex (PFC) working-memory (WM) deficits seen in schizophrenia. Dr. Thuault will investigate the sustained firing of PFC neurons and explore the potential alteration of this activity in two mutant mice with contrasting alterations in WM. The first line has a forebrain-restricted deletion of HCN1 and shows enhanced spatial WM. The second line— a model of schizophrenia—overexpresses dopamine D2 receptors in the striatum, resulting in alterations in prefrontal dopaminergic transmission and deficits in WM and behavioral flexibility. Dr. Thuault will electrophysiologically characterize the properties of PFC neurons in brain slices of control and mutant animals and compare the ability of the neurons to undergo and maintain persistent firing in the two lines. The effect of dopamine on persistent activity in the two strains will also be studied. The approach could lead to drugs targeting cognitive symptoms in schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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