1. Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses
- Author
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Besnard, Antoine, Gao, Yuan, TaeWoo Kim, Michael, Twarkowski, Hannah, Reed, Alexander Keith, Langberg, Tomer, Feng, Wendy, Xu, Xiangmin, Saur, Dieter, Zweifel, Larry S, Davison, Ian, and Sahay, Amar
- Subjects
Biological Psychology ,Biomedical and Clinical Sciences ,Psychology ,Basic Behavioral and Social Science ,Neurosciences ,Mental Health ,Behavioral and Social Science ,Adaptation ,Psychological ,Animals ,Anxiety ,CA3 Region ,Hippocampal ,Conditioning ,Classical ,Dentate Gyrus ,Discrimination ,Psychological ,Fear ,Freezing Reaction ,Cataleptic ,Interneurons ,Male ,Mice ,Neural Pathways ,Optogenetics ,Septal Nuclei ,Somatostatin ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - 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.
- Published
- 2019