Project Summary

Surojit Paul, Ph.D. (Young Investigator 2004) of Yale Child Study Center/Yale University, proposes studying in the rat a particular aspect of the biochemistry of fear conditioning in the amygdala, a region of the brain known to play a central role in both normal fear and pathological anxiety. The aim of this project is to determine the effect of STEP, a striatal enriched phosphatase, on the regulation of ERK/MAP kinase and its consequence on the acquisition of conditioned fear in a rat. Changes in the phosphorylation of STEP and its co-localization with p-ERK in the amygdala will be assessed by immunohistochemistry and immunoblotting with antibodies to phospho-STEP and phospho-ERK. Dr. Surojit will then disrupt fear conditioning by disrupting normal STEP-ERK interactions. Bilateral tubes will be implanted into the basolateral amygdala to allow infusion of a mutant STEP protein. Dr. Surojit hypothesizes that infusion of mutant STEP will attenuate fear conditioning by blocking activation of ERK and its nuclear translocation. He will also infuse a second protein that prevents STEP from interacting with ERK. We hypothesize that this second infusion will enhance fear conditioning.

Program Area: MULTIPLE FOCUS AREAS\Anxiety Disorders/Unipolar Depression

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