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Science 306 (5697): 882-884

Copyright © 2004 by the American Association for the Advancement of Science

Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

S. G. Birnbaum,1,2 P. X. Yuan,3 M. Wang,1 S. Vijayraghavan,1 A. K. Bloom,1 D. J. Davis,1 K. T. Gobeske,1 J. D. Sweatt,2 H. K. Manji,3 A. F. T. Arnsten1*

Abstract: The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

1 Department of Neurobiology, Yale Medical School, 333 Cedar Street, New Haven, CT 06520–8001, USA.
2 Department of Neuroscience, 1 Baylor Plaza, Baylor College of Medicine, Houston TX 77030, USA.
3 Laboratory of Molecular Pathophysiology, National Institute of Mental Health (NIMH), Bethesda, MD 20892–4405, USA.

* To whom correspondence should be addressed. E-mail: amy.arnsten{at}

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