The basolateral amygdala is necessary for learning but not relearning extinction of context conditioned fear.
Extinction of conditioned fear involves new learning that inhibits but does not eliminate the original fear memory. This inhibitory learning is thought to require activation of NMDA receptors (NMDAr) within the basolateral amygdala (BLA). However, once extinction has been learned, the role played by the BLA during subsequent extinction procedures remains unknown. The present study examined the role of neuronal activity and NMDAr activation in rats receiving their first or second extinction of context fear. We found that BLA infusion of DL-APV, a competitive antagonist of NMDAr, depressed fear responses at both the first and second extinction. It impaired learning extinction but spared and even facilitated relearning extinction. BLA infusion of muscimol, a GABA(A) agonist, produced a similar outcome, suggesting that DL-APV not only blocked NMDAr-dependent plasticity but also disrupted neuronal activity. In contrast, infusion of ifenprodil, a more selective antagonist of NMDAr containing the NR2B subunit, did not depress fear responses but impaired short- and long-term inhibition of fear at both the first and second extinction. Therefore, we suggest that relearning extinction normally requires NMDAr containing the NR2B subunit in the BLA. However, simultaneous blockade of these receptors and neuronal activity in the BLA results in compensatory learning that is able to promote long-term re-extinction. These data are consistent with a current model that attributes fear extinction to interactions between several neural substrates, including the amygdala and the medial prefrontal cortex.
Laurent
Vincent
V
School of Psychology, The University of New South Wales, Sydney, New South Wales 2052, Australia.
Marchand
Alain R
AR
Westbrook
R Frederick
RF
D000679:Amygdala / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D018755:GABA Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol