Project Summary

John E. Lisman, Ph.D. (Distinguished Investigator 2003) of Brandeis University, is studying how deficits in the NMDA receptor can produce behavioral symptoms of schizophrenia.  NMDA receptors generate voltage-dependent postsynaptic potentials (EPSPs), and Dr. Lisman's prior work shows that the time course and voltage-dependence of these EPSPs enables them to perform network computations important in cognitive processing.  These EPSPs may play a special role in recall in the hippocampus, a brain region implicated in schizophrenia and would allow for some specific and testable predictions about memory abnormalities in schizophrenia.  Dr. Lisman has developed a computational model of sequence learning and recall which can reproduce several key experimental results and makes testable predictions regarding the role of NMDA channels.  Based on past research using this model, Dr. Lisman believes that if NMDA channels are compromised in schizophrenia, very specific deficits in the recall of sequences will result.  If NMDA channels are compromised in schizophrenia, very specific deficits in the recall of sequences with crossing paths (this occurs when two stores sequence have common elements) are predicted.  These deficits should be detectable using quantifiable list learning tests.  Dr. Lisman hopes this work will yield several outcomes:  a very sensitive test for schizophrenia (normal subjects make virtually no errors at crossing paths); results will help in the development of a biophysically based network model of hippocampal function; and the particular pattern of abnormalities detected in this research will focus future work on NMDA channels and dopamine modulation at specific synapses.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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