Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses
Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses
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DOI：
10.1038/s41593-018-0330-y
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发表时间：
2019-03-01
影响因子：
25
通讯作者：
Sahay, Amar
中科院分区：
文献类型：
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作者：
Besnard, Antoine;Gao, Yuan;Sahay, Amar
对外部威胁的适应性恐惧反应依赖于将上下文编码的计算有效中继到皮层下电路。对情境恐惧辨别后高度共激活的整体进行全脑分析，发现背外侧隔膜 (DLS) 是齿状回-CA3 回路的中继。逆行单突触追踪和电生理全细胞记录表明，表达 DLS 生长抑素的中间神经元 (SST-IN) 接收直接 CA3 输入。在清醒、有行为的小鼠中，DLS SST-IN 的纵向体内钙成像发现，在环境调节过程中，有一个稳定的足部电击反应性 SST-IN 群体，其活动在随后的训练环境中（但不是在类似的中性环境或开放场中）回忆过程中跟踪和预测非冻结时期。 DLS SST-IN 的光遗传学衰减或刺激双向调节条件性恐惧反应并招募近端和远端皮质下目标。总之，这些观察结果表明，潜在的硬连线 DLS SST-IN 亚群作为流动性仲裁者的作用，可以校准适合情境的行为恐惧反应。
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.