Extinguishing trace fear engages the retrosplenial cortex rather than the amygdala. Neurobiol Learn Mem 2014 Sep;113:41-54
Date
09/24/2013Pubmed ID
24055593Pubmed Central ID
PMC3959632DOI
10.1016/j.nlm.2013.09.007Scopus ID
2-s2.0-84902120286 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
Extinction learning underlies the treatment for a variety of anxiety disorders. Most of what is known about the neurobiology of extinction is based on standard "delay" fear conditioning, in which awareness is not required for learning. Little is known about how complex, explicit associations extinguish, however. "Trace" conditioning is considered to be a rodent model of explicit fear because it relies on both the cortex and hippocampus and requires explicit contingency awareness in humans. Here, we explore the neural circuit supporting trace fear extinction in order to better understand how complex memories extinguish. We first show that the amygdala is selectively involved in delay fear extinction; blocking intra-amygdala glutamate receptors disrupted delay, but not trace extinction. Further, ERK phosphorylation was increased in the amygdala after delay, but not trace extinction. We then identify the retrosplenial cortex (RSC) as a key structure supporting trace extinction. ERK phosphorylation was selectively increased in the RSC following trace extinction and blocking intra-RSC NMDA receptors impaired trace, but not delay extinction. These findings indicate that delay and trace extinction require different neural circuits; delay extinction requires plasticity in the amygdala whereas trace extinction requires the RSC. Anxiety disorders linked to explicit memory may therefore depend on cortical processes that have not been traditionally targeted by extinction studies based on delay fear.
Author List
Kwapis JL, Jarome TJ, Lee JL, Gilmartin MR, Helmstetter FJAuthor
Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AmygdalaAnimals
Behavior, Animal
Cerebral Cortex
Extinction, Psychological
Extracellular Signal-Regulated MAP Kinases
Fear
Male
Rats
Rats, Long-Evans
Receptors, N-Methyl-D-Aspartate
Valine
