Extinguishing trace fear engages the retrosplenial cortex rather than the amygdala

Janine Kwapis, Timothy J. Jarome, Jonathan L. Lee, Marieke R. Gilmartin, Fred J. Helmstetter

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)41-54
Number of pages14
JournalNeurobiology of Learning and Memory
Volume113
DOIs
StatePublished - Jan 1 2014

Fingerprint

Amygdala
Fear
Anxiety Disorders
Psychological Extinction
Phosphorylation
Learning
Neurobiology
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Rodentia
Hippocampus

All Science Journal Classification (ASJC) codes

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

Kwapis, Janine ; Jarome, Timothy J. ; Lee, Jonathan L. ; Gilmartin, Marieke R. ; Helmstetter, Fred J. / Extinguishing trace fear engages the retrosplenial cortex rather than the amygdala. In: Neurobiology of Learning and Memory. 2014 ; Vol. 113. pp. 41-54.
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Extinguishing trace fear engages the retrosplenial cortex rather than the amygdala. / Kwapis, Janine; Jarome, Timothy J.; Lee, Jonathan L.; Gilmartin, Marieke R.; Helmstetter, Fred J.

In: Neurobiology of Learning and Memory, Vol. 113, 01.01.2014, p. 41-54.

Research output: Contribution to journalArticle

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