Prelimbic BDNF and TrkB signaling regulates consolidation of both appetitive and aversive emotional learning

• Type of Material: Article
• Authors: Dennis W Choi, Emory University; Shannon L Gourley, Emory University; Kerry Ressler, Emory University
• Language: English
• Date: 2012-12-18
• Publisher: Nature Publishing Group: Open Access Journals - Option B
• Publication Version: Final Published Version
• Copyright Statement: © 2011 Choi et al.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://www.nature.com/tp/journal/v2/n12/full/tp2012128a.html
• Title of Journal or Parent Work: Translational Psychiatry
• ISSN: 2158-3188
• Volume: 2012
• Issue: 2
• Start Page: e205
• End Page: e205
• Grant/Funding Information: This study was supported by the National Institutes of Health (F32MH085443, R01DA01962), the Center for Behavioral Neuroscience (NSF agreement IBN-987675), the Burroughs Wellcome Fund, the National Institutes of Health/NCRR base grant (P51RR000165) to Yerkes National Primate Research Center, and Children's Health care of Atlanta.
• Keywords: BDNF; mPFC; fear; TrkB; prelimbic cortex; appetitive
• Research Categories: Biology, Neuroscience

Abstract

The medial prefrontal cortex (mPFC) is known to regulate executive decisions and the expression of emotional memories. More specifically, the prelimbic cortex (PL) of the mPFC is implicated in driving emotional responses via downstream targets including the nucleus accumbens and amygdala, but mechanisms are yet to be fully understood. Therefore, we investigated whether prelimbic cortical brain-derived neurotrophic factor (BDNF) signaling through the high-affinity tyrosine kinase receptor B (TrkB) receptor may serve as a molecular mechanism underlying emotional memory encoding. Here, we utilized viral-mediated inducible bdnf deletion within the PL, as well as TrkBF616A mutant mice, wherein TrkB receptor point mutation results in its being highly sensitive to inhibition by small PP1-derivative molecules, serving as a specific TrkB inhibitor. The site-specific TrkB antagonism and viral-mediated bdnf deletion within the PL resulted in deficits in both cocaine-dependent associative learning and fear expression. Deficiencies were rescued by the novel TrkB agonist 7,8-dihydroxyflavone, indicating that PL BDNF expression and downstream signaling through the TrkB receptor are required for memory formation in both appetitive and aversive domains.