Project Summary

M. Margarita Behrens, Ph.D. (Young Investigator 2004) of the Scripps Research Institute, aims to understand why blocking NMDA glutamate receptor activity with antagonist drugs, such as PCP or ketamine, besides decreasing the activity of neurons expressing the receptors, such as cortical and hippocampal pyramidal neurons, leads to increasing behavioral and cognitive activation associated with psychosis. Dr. Behrens hypothesizes NMDA receptors are not only expressed on excitatory neurons but are also expressed in inhibitory circuits, such as the GABAergic pathway. Thus, reduced NMDA-dependent excitation acting on an inhibitory input could result in less inhibition and possible activation. One of the key cortical GABAergic systems is the parvalbumin-positive chandelier cells, which may have impaired function in schizophrenia. Chandelier cells produce a wide-spread and effective inhibition of the cortical network output. Dr. Behrens proposes testing whether chandelier GABAergic interneurons have a specific response to excitatory glutamatergic neurotransmission that differs from pyramidal neurons, a finding that may underlie the acute psychotic effects of NMDA receptor antagonists.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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