Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex.
Extinction of conditioned fear is an active learning process requiring N-methyl-D-aspartate receptors (NMDARs), but the timing, location, and neural mechanisms of NMDAR-mediated processing in extinction are a matter of debate. Here we show that infusion of the NMDAR antagonist CPP into the ventromedial prefrontal cortex (vmPFC) prior to, or immediately after, extinction training impaired 24 hr recall of extinction. These findings indicate that consolidation of extinction requires posttraining activation of NMDARs within the vmPFC. Using multichannel unit recording, we observed that CPP selectively reduced burst firing in vmPFC neurons, suggesting that bursting in vmPFC is necessary for consolidation of extinction. In support of this, we found that the degree of bursting in infralimbic vmPFC neurons shortly after extinction predicted subsequent recall of extinction. We suggest that NMDAR-dependent bursting in the infralimbic vmPFC initiates calcium-dependent molecular cascades that stabilize extinction memory, thereby allowing for successful recall of extinction.
Burgos-Robles
Anthony
A
Department of Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732.
Vidal-Gonzalez
Ivan
I
Santini
Edwin
E
Quirk
Gregory J
GJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid