A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats

Christina A. Sanford, Marta E. Soden, Madison A. Baird, Samara M. Miller, Jay Schulkin, Richard D. Palmiter, Michael Clark, Larry S. Zweifel

Research output: Contribution to journalArticlepeer-review


Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing.

Original languageEnglish (US)
Pages (from-to)164-178
Number of pages15
Issue number1
StatePublished - Jan 4 2017
Externally publishedYes


  • CRF
  • GABA
  • LTP
  • central amygdala
  • circuits
  • differential fear conditioning
  • fear
  • plasticity
  • threat

ASJC Scopus subject areas

  • Neuroscience(all)


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