Project Summary

Stanislav Zakharenko, Ph.D. (Young Investigator 2004) of Columbia University, aims to study synaptic function in three animals each carrying different mutations in certain regions of a chromosome associated with schizophrenia (SZ) susceptibility genes. He will focus on microdeletions of 22q11, which represents one of the highest known genetic risk factors for the development of SZ. One of the mouse srains carries the entire SZ-associated microdeletion. The others strains target genes within the microdeletion: the transmembrane palmitoyltransferase-encoding KIAA1292 and the proline dehyrrogenase-encoding PRODH. Using a combination of electrophysiological and multi-photon imaging techniques, Dr. Zakharenko will test if the animals have deficits in synaptic transmission and synaptic plasticity at excitatory synapses between certain pyramidal neurons in the hippocampus. He can also evaluate changes in number, morphology and function of dendritic spines in the pyramidal neurons. Results could lead to a better understanding of synaptic dysfunction and pathophysiology in SZ and new potential treatment strategies.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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