Project Summary

Zachary F. Mainen, Ph.D. (Independent Investigator 2004) of Cold Spring Harbor Laboratory, proposes using a novel method, single neuron cell recording, to test in the cortex of awake rats the effects on neurotransmission of ketamine, an abused substance that can produce schizophrenia-like symptoms in humans. Evidence suggests ketamine produces its psychotomimetic effects by possibly blocking the NMDA glutamate receptors on inhibitory neurons in the prefrontal cortex. The hypothesis can explain why blocking an excitatory receptor is a can decrease prefrontal activity. This hypothesis can also link the NMDA receptor hypofunction theory of schizophrenia with evidence for reductions in GABA function in human schizophrenics. In the proposed study, Dr. Mainen will research the role of the neurotransmitters glutamate and GABA in the neural pathology underlying schizophrenia. Early results reveal that the laboratory can distinguish inhibitory interneurons and excitatory pyramidal neurons on the basis of their spike waveforms. They also demonstrate that the lab can assay local inhibitory circuits. These established metrics should allow directly testing of the hypothesis that NMDA receptor antagonists (ketamine) disrupt the functioning of neocortical circuitry by suppressing the activity of fast-spiking GABAergic interneurons.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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