Prefrontal inputs to the amygdala instruct fear extinction memory formation.
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.
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20853, USA. ; Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Olena
O
Bukalo
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20853, USA.
Courtney R
CR
Pinard
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20853, USA. ; Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Shana
S
Silverstein
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82/III, A-6020 Innsbruck, Austria.
Christina
C
Brehm
Department of Psychiatry and Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Nolan D
ND
Hartley
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82/III, A-6020 Innsbruck, Austria.
Nigel
N
Whittle
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20853, USA.
Giovanni
G
Colacicco
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20853, USA.
Erica
E
Busch
Department of Psychiatry and Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Sachin
S
Patel
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82/III, A-6020 Innsbruck, Austria.
Nicolas
N
Singewald
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20853, USA.
Andrew
A
Holmes