Besnard, AntoineGao, YuanKim, Michael TaeWooTwarkowski, HannahReed, Alexander KeithLangberg, TomerFeng, WendyXu, XiangminSaur, DieterZweifel, Larry S.Davison, IanSahay, Amar2023-08-222023-08-222019-03-01A. 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-y1097-62561546-1726https://hdl.handle.net/2144/46578Adaptive 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.p. 436-Print-ElectronicenScience & technologyLife sciences & biomedicineNeurosciencesNeurosciences & neurologyLateral septumUnit-activityAmygdalaAnxietyHippocampusMemoryDynamicsCircuitNeuronsDorsalPsychologyCognitive sciencesNeurology & neurosurgeryBiological psychologyAdaptation, psychologicalAnimalsAnxietyCA3 Region, HippocampalConditioning, classicalDentate gyrusDiscrimination, psychologicalFearFreezing reaction, catalepticInterneuronsMaleMiceNeural pathwaysOptogeneticsSeptal nucleiSomatostatinDiscrimination (psychology)Article2023-02-1410.1038/s41593-018-0330-y0000-0002-0929-8873 (Besnard, Antoine)0000-0003-0998-7676 (Davison, Ian)435994