Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses.
Antoine BesnardYuan GaoMichael TaeWoo KimHannah TwarkowskiAlexander Keith ReedTomer LangbergWendy FengXiangmin XuDieter SaurLarry S ZweifelIan DavisonAmar SahayPublished in: Nature neuroscience (2019)
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.
Keyphrases
- prefrontal cortex
- white matter
- minimally invasive
- working memory
- high resolution
- transcranial direct current stimulation
- stem cells
- single cell
- mesenchymal stem cells
- metabolic syndrome
- type diabetes
- deep brain stimulation
- drug delivery
- protein kinase
- brain injury
- neuroendocrine tumors
- high fat diet induced
- skeletal muscle
- wild type
- cerebral ischemia
- adipose tissue