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Author Notes:

To whom correspondence should be addressed. E-mail: kressle@emory.edu.

Edited by David J. Anderson, California Institute of Technology, Pasadena, CA, and approved December 31, 2009 (received for review August 17, 2009)

Author contributions: D.C.C., K.M.M., and K.J.R. designed research; D.C.C., K.A.M., S.-W.J., and K.M.M. performed research; K.Y. and S.-W.J. contributed new reagents/analytic tools; D.C.C., K.A.M., K.Y., S.-W.J., K.M.M., and K.J.R. analyzed data; and D.C.C. and K.J.R. wrote the paper.

We thank Dr. Mary Nguyen-Choi for her expertise with the preparation of manuscript figures and Dr. Lisa Stanek for her experimental and technical expertise.

The authors declare no conflict of interest.

Subjects:

Research Funding:

National Institutes of Health

National Science Foundation

Center for Behavioral Neuroscience

National Alliance for Research on Schizophrenia and Depression

Burroughs Wellcome Fund

Keywords:

  • learning
  • plasticity
  • prefrontal cortex
  • Cre/LoxP
  • inducible knockout

Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 107, Number 6

Publisher:

, Pages 2675-2680

Type of Work:

Article | Post-print: After Peer Review

Abstract:

In the medial prefrontal cortex, the prelimbic area is emerging as a major modulator of fear behavior, but the mechanisms remain unclear. Using a selective neocortical knockout mouse, virally mediated prelimbic cortical-specific gene deletion, and pharmacological rescue with a TrkB agonist, we examined the role of a primary candidate mechanism, BDNF, in conditioned fear. We found consistently robust deficits in consolidation of cued fear but no effects on acquisition, expression of unlearned fear, sensorimotor function, and spatial learning. This deficit in learned fear in the BDNF knockout mice was rescued with systemic administration of a TrkB receptor agonist, 7,8-dihydroxyflavone. These data indicate that prelimbic BDNF is critical for consolidation of learned fear memories, but it is not required for innate fear or extinction of fear. Moreover, use of site-specific, inducible BDNF deletions shows a powerful mechanism that may further our understanding of the pathophysiology of fear-related disorders.

Copyright information:

© 2010 National Academy of Sciences

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