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Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses.

  • Author(s): Besnard, Antoine;
  • Gao, Yuan;
  • TaeWoo Kim, Michael;
  • Twarkowski, Hannah;
  • Reed, Alexander Keith;
  • Langberg, Tomer;
  • Feng, Wendy;
  • Xu, Xiangmin;
  • Saur, Dieter;
  • Zweifel, Larry S;
  • Davison, Ian;
  • Sahay, Amar
  • et al.
Abstract

Adaptive fear responses to external threats rely upon efficient relay of computations underlying contextual encoding to subcortical circuits. Brain-wide analysis of highly coactivated ensembles following contextual fear discrimination identified the dorsolateral septum (DLS) as a relay of the dentate gyrus-CA3 circuit. Retrograde monosynaptic tracing and electrophysiological whole-cell recordings demonstrated that DLS somatostatin-expressing interneurons (SST-INs) receive direct CA3 inputs. Longitudinal in vivo calcium imaging of DLS SST-INs in awake, behaving mice identified a stable population of footshock-responsive SST-INs during contextual conditioning whose activity tracked and predicted non-freezing epochs during subsequent recall in the training context but not in a similar, neutral context or open field. Optogenetic attenuation or stimulation of DLS SST-INs bidirectionally modulated conditioned fear responses and recruited proximal and distal subcortical targets. Together, these observations suggest a role for a potentially hard-wired DLS SST-IN subpopulation as arbiters of mobility that calibrate context-appropriate behavioral fear responses.

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