Bukalo O, Pinard CR, Silverstein S, Brehm C, Hartley ND, Whittle N, Colacicco G, Busch E, Patel S, Singewald N, Holmes A. Prefrontal inputs to the amygdala instruct fear extinction memory formation. Science advances. 2015 Jul;1(1). PMID: 26504902 [PubMed] PMCID: PMC4618669 NIHMSID: NIHMS725274.
Persistent anxiety after a psychological trauma is a hallmark of many anxiety disorders. However, the neural circuits mediating the extinction of traumatic fear memories remain incompletely understood. We show that selective, in vivo stimulation of the ventromedial prefrontal cortex (vmPFC)-amygdala pathway facilitated extinction memory formation, but not retrieval. Conversely, silencing the vmPFC-amygdala pathway impaired extinction formation and reduced extinction-induced amygdala activity. Our data demonstrate a critical instructional role for the vmPFC-amygdala circuit in the formation of extinction memories. These findings advance our understanding of the neural basis of persistent fear, with implications for posttraumatic stress disorder and other anxiety disorders.