Project Summary

German Barrionuevo, M.D. (Independent Investigator 2002) of University of Pittsburgh, notes that pathological dysfunctions that disrupt the intrinsic circuitry of the dorsolateral prefrontal cortex (DLPFC) have been implicated in schizophrenia.  Cognitive dysfunctions in schizophrenia are characterized by a loss of working memory, such as the inability to maintain a line on a bit of information in order to guide a subsequent response.   In monkeys, pyramidal neurons in the DLPFC exhibit sustained firing during the delay period of delayed-response tasks, and this activity has been proposed to constitute the cellular basis of working memory.  Working memory also depends upon an optimal level of dopamine (DA) receptor stimulation in DLPFC.  Dr. Barrionuevo will investigate the input dynamics of long-range connectivity and the contribution of postsynaptic calcium signaling to short-term synaptic plasticity.  He will also focus on how the synaptic potentials recorded at the soma and the influx of calcium are modulated in the presence of DA.  He hypothesizes that natural train stimulation DA or a specific D1 receptor agonist will amplify the current through NMDA receptors, thus leading to a larger influx in postsynaptic calcium.  Futhermore, since DA increases the intrinsic excitability of pyramidal cell, he expects that the combined action of DA on the intrinsic excitability and the NMDA-medidated synaptic depolarization may increase the output of pyramidal cell.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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