Optogenetic silencing of a corticotropin-releasing factor pathway from the central amygdala to the bed nucleus of the stria terminalis disrupts sustained fear

Mol Psychiatry. 2018 Apr;23(4):914-922. doi: 10.1038/mp.2017.79. Epub 2017 Apr 25.


The lateral central nucleus of the amygdala (CeAL) and the dorsolateral bed nucleus of the stria terminalis (BNSTDL) coordinate the expression of shorter- and longer-lasting fears, respectively. Less is known about how these structures communicate with each other during fear acquisition. One pathway, from the CeAL to the BNSTDL, is thought to communicate via corticotropin-releasing factor (CRF), but studies have yet to examine its function in fear learning and memory. Thus, we developed an adeno-associated viral-based strategy to selectively target CRF neurons with the optogenetic silencer archaerhodopsin tp009 (CRF-ArchT) to examine the role of CeAL CRF neurons and projections to the BNSTDL during the acquisition of contextual fear. Expression of our CRF-ArchT vector injected into the amygdala was restricted to CeAL CRF neurons. Furthermore, CRF axonal projections from the CeAL clustered around BNSTDL CRF cells. Optogenetic silencing of CeAL CRF neurons during contextual fear acquisition disrupted retention test freezing 24 h later, but only at later time points (>6 min) during testing. Silencing CeAL CRF projections in the BNSTDL during contextual fear acquisition produced a similar effect. Baseline contextual freezing, the rate of fear acquisition, freezing in an alternate context after conditioning and responsivity to foot shock were unaffected by optogenetic silencing. Our results highlight how CeAL CRF neurons and projections to the BNSTDL consolidate longer-lasting components of a fear memory. Our findings have implications for understanding how discrete amygdalar CRF pathways modulate longer-lasting fear in anxiety- and trauma-related disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Anxiety / metabolism
  • Central Amygdaloid Nucleus / metabolism*
  • Conditioning, Classical
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Fear / physiology*
  • Male
  • Memory / physiology
  • Neurons / metabolism
  • Optogenetics / methods
  • Rats
  • Rats, Inbred SHR
  • Septal Nuclei / metabolism*
  • Thalamus / metabolism


  • Corticotropin-Releasing Hormone