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

Antoine Besnard, Yuan Gao, Michael TaeWoo Kim, Hannah Twarkowski, Alexander Keith Reed, Tomer Langberg, Wendy Feng, Xiangmin Xu, Dieter Saur, Larry S. Zweifel, Ian Davison, Amar Sahay

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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.

Original languageEnglish
Pages (from-to)436-446
Number of pages11
JournalNature Neuroscience
Volume22
Issue number3
DOIs
StatePublished - 1 Mar 2019

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