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Science 304 (5672): 881-883

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

The Involvement of the Anterior Cingulate Cortex in Remote Contextual Fear Memory

Paul W. Frankland,1,2,3* Bruno Bontempi,4* Lynn E. Talton,1 Leszek Kaczmarek,1,5 Alcino J. Silva1{dagger}

Abstract: Although the molecular, cellular, and systems mechanisms required for initial memory processing have been intensively investigated, those underlying permanent memory storage remain elusive. We present neuroanatomical, pharmacological, and genetic results demonstrating that the anterior cingulate cortex plays a critical role in remote memory for contextual fear conditioning. Imaging of activity-dependent genes shows that the anterior cingulate is activated by remote memory and that this activation is impaired by a null {alpha}-CaMKII mutation that blocks remote memory. Accordingly, reversible inactivation of this structure in normal mice disrupts remote memory without affecting recent memory.

1 Departments of Neurobiology, Psychiatry, Psychology and Brain Research Institute, UCLA, 695 Charles Young Drive South, Los Angeles, CA 90095–1761, USA.
2 Department of Integrative Biology, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
3 Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
4 Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Avenue des Facultés, 33405 Talence, France.
5 Nencki Institute, Pasteura 3, 02–093, Warsaw, Poland.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: silvaa{at}

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