Journal
NATURE NEUROSCIENCE
Volume 22, Issue 3, Pages 436-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-018-0330-y
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Funding
- 2014 NARSAD Young Investigator Award
- Bettencourt-Schueller Foundation
- Philippe Foundation
- 2016 MGH ECOR Fund for Medical Discovery (FMD)
- 2013 HSCI Harvard Internship Program Award
- 2017 HSCI Harvard Internship Program Award
- NIH Biobehavioral Research Awards for Innovative New Scientists (BRAINS) [R01MH104175]
- Ellison Medical Foundation
- Whitehall Foundation
- Inscopix Decode award
- NARSAD Independent Investigator Award
- Blue Guitar Fund
- Harvard Neurodiscovery Center-MADRC Center Pilot Grant award
- Alzheimer's Association Research Grant
- Harvard Stem Cell Institute Development grant
- HSCI seed grant
- [NIH-R01AG048908]
- [NIH-1R01MH111729]
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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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