Project Summary

Tracie Ann Paine, Ph.D. (Young Investigator 2006) of Harvard Medical School, will use a rat model to study the molecular biology of attention deficits seen in schizophrenia. Attention deficits in schizophrenia probably contribute to the thought disorder and psychosis characteristic of this condition. Evidence suggests altered Dl receptor activity in the medial prefrontal cortex (mPFC) may underlie the observed attention deficits. Dl receptor activation stimulates cyclic AMP-dependent protein kinase (PKA), which activates the transcription factor cyclic AMP response element-binding protein (CREB). CREB regulates a number of proteins. Thus, altering the PKA-CREB signaling pathway may affect attention. Attention can be measured in rats with a serial reaction-time task. Dr. Paine proposes to alter PKA-CREB signaling within the mPFC of rats and assess their performance in a reaction-time task. She will change PKA activity by local microinjection of either a PKA activator or inhibitor. She also will alter CREB function by transfecting cells with either a wild-type or a mutant CREB gene. Results should shed light on how the PKA-CREB signaling pathway mediates the attention deficits observed in schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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