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


Authors: 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
Publication: Nature Neuroscience
Date: February 4, 2019
Link to article: https://www.nature.com/articles/s41593-018-0330-y?__hssc=91116613.71.1608871335…


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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