title: Fear extinction learning can be impaired or enhanced by modulation of the CRF system in the basolateral nucleus of the amygdala.
abstract: The neuropeptide corticotropin-releasing factor (CRF) is released during periods of anxiety and modulates learning and memory formation. One region with particularly dense concentrations of CRF receptors is the basolateral nucleus of the amygdala (BLA), a critical structure for both Pavlovian fear conditioning and fear extinction. While CRF has the potential to modify amygdala-dependent learning, its effect on fear extinction has not yet been assessed. In the present study, we examined the modulatory role of CRF on within-session extinction and fear extinction consolidation. Intra-BLA infusions of the CRF binding protein ligand inhibitor CRF(6-33) which increases endogenous levels of free CRF, or intra-BLA infusions of exogenous CRF made prior to fear extinction learning did not affect either fear expression or within-session extinction learning. However, when these animals were tested twenty-four hours later, drug free, they showed impairments in extinction memory. Conversely, intra-BLA infusions of the CRF receptor antagonist α-helical CRF(9-41) enhanced memory of fear extinction. These results suggest that increased CRF levels within the BLA at the time of fear extinction learning actively impair the consolidation of long-term fear extinction.
authors.affiliation: Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, United States.
authors.forename: Dina
authors.initials: D
authors.lastname: Abiri
authors.affiliation: Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, United States.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Douglas
authors.affiliation: Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, United States.
authors.forename: Katina C
authors.initials: KC
authors.lastname: Calakos
authors.affiliation: Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, United States.
authors.forename: Georgia
authors.initials: G
authors.lastname: Barbayannis
authors.affiliation: Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Roberts
authors.affiliation: Barnard College, Columbia University, 3009 Broadway, New York, NY 10027, United States. Electronic address: ebauer@barnard.edu.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Bauer
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003346:Corticotropin-Releasing Hormone
keywords: Amygdala; Anxiety; Corticotropin-releasing factor; Fear extinction; Fear learning