Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses
Date
2019-03-01
Authors
Besnard, Antoine
Gao, Yuan
Kim, Michael TaeWoo
Twarkowski, Hannah
Reed, Alexander Keith
Langberg, Tomer
Feng, Wendy
Xu, Xiangmin
Saur, Dieter
Zweifel, Larry S.
Version
Accepted manuscript
OA Version
Citation
A. Besnard, Y. Gao, M.T. Kim, H. Twarkowski, A.K. Reed, T. Langberg, W. Feng, X. Xu, D. Saur, L.S. Zweifel, I. Davison, A. Sahay. 2019. "Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses" Nature Neuroscience, Volume 22, Issue 3, pp.436-+. https://doi.org/10.1038/s41593-018-0330-y
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.