Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Cell Rep. 2024 Nov 26;43(11):114880. doi: 10.1016/j.celrep.2024.114880. Epub 2024 Oct 18.
Contextual memories are critical for survival but must be extinguished when new conditions render them nonproductive. By most accounts, extinction forms a new memory that competes with the original association for control over behavior, but the underlying circuit mechanisms remain largely enigmatic. Here, we demonstrate that extinction of contextual fear conditioning recruits somatostatin interneurons (SST-INs) in the ventral hippocampus. Correspondingly, real-time activity of SST-INs correlates with transitions between immobility and movement, signaling exit from defensive freezing bouts. Optogenetic manipulation of SST-INs but not parvalbumin interneurons (PV-INs) elicits bidirectional changes in freezing that are specific to the context in which extinction was acquired. Finally, similar effects were obtained following extinction of sucrose-based appetitive conditioning, in which SST-IN inhibition triggers relapse to reward seeking. These data suggest that ventral hippocampal SST-INs play a fundamental role in extinction that is independent of affective valence and may be related to their disruption of spontaneous emotional responses.
情景记忆对于生存至关重要，但当新情况使其变得低效时，必须将其消除。根据大多数说法，消除会形成一种新的记忆，这种记忆与原始联想竞争以控制行为，但潜在的电路机制在很大程度上仍然是个谜。在这里，我们证明了情景恐惧条件反射的消除会招募腹侧海马体中的生长抑素中间神经元（SST-IN）。相应地，SST-IN 的实时活动与从不动到运动的转变相关，表明退出防御性冻结发作。SST-IN 的光遗传学操纵而不是 PV-IN 会引起特定于获得消除的上下文的冻结的双向变化。最后，在基于蔗糖的食欲条件反射的消除后也获得了类似的效果，其中 SST-IN 抑制会引发对寻求奖励的复发。这些数据表明，腹侧海马体 SST-IN 在消除中起着至关重要的作用，而与情感价值无关，并且可能与它们对自发情绪反应的破坏有关。
