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Nat Neurosci. 2019 Mar;22(3):436-446. doi: 10.1038/s41593-018-0330-y. Epub 2019 Feb 4.

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

Besnard A1,2,3,4, Gao Y5, TaeWoo Kim M1,2,3,4, Twarkowski H1,2,3,4, Reed AK1,2,3,4, Langberg T1,2,3,4, Feng W1,2,3,4, Xu X6, Saur D7,8, Zweifel LS9, Davison I5, Sahay A10,11,12,13.

Author information

1
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
2
Harvard Stem Cell Institute, Cambridge, MA, USA.
3
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
4
BROAD Institute of Harvard and MIT, Cambridge, MA, USA.
5
Department of Biology, Boston University, Boston, MA, USA.
6
Departments of Anatomy and Neurobiology and Biomedical Engineering, School of Medicine, University of California, Irvine, CA, USA.
7
Division of Translational Cancer Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany.
8
Institute of Translational Cancer Research and Experimental Cancer Therapy, and Department of Medicine II, Technische Universit├Ąt Munchen, Munich, Germany.
9
Department of Psychiatry and Behavioral Science, University of Washington, Seattle, WA, USA.
10
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA. asahay@mgh.harvard.edu.
11
Harvard Stem Cell Institute, Cambridge, MA, USA. asahay@mgh.harvard.edu.
12
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. asahay@mgh.harvard.edu.
13
BROAD Institute of Harvard and MIT, Cambridge, MA, USA. asahay@mgh.harvard.edu.

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.

PMID:
30718902
PMCID:
PMC6387640
[Available on 2019-08-04]
DOI:
10.1038/s41593-018-0330-y

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