Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear.
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.
Department of Psychiatry and Behavioral Sciences, Howard Hughes Medical Institute, Center for Behavioral Neuroscience, Emory University School of Medicine, Atlanta, GA 30322, USA.
Dennis C
DC
Choi
Kimberly A
KA
Maguschak
Keqiang
K
Ye
Sung-Wuk
SW
Jang
Karyn M
KM
Myers
Kerry J
KJ
Ressler
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects; D005108:Extinction, Psychological; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D005260:Female; D047309:Flavones / Q000494:pharmacology; D017403:In Situ Hybridization; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000378:metabolism; D020813:Receptor, trkB / Q000819:agonists / Q000502:physiology
C485383:6,7-dihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D047309:Flavones; D020813:Receptor, trkB