F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02215, USA.
Cell Rep. 2022 Oct 25;41(4):111521. doi: 10.1016/j.celrep.2022.111521.
Sudden unexpected environmental changes capture attention and, when perceived as potentially dangerous, evoke defensive behavioral states. Perturbations of the lateral septum (LS) can produce extreme hyperdefensiveness even to innocuous stimuli, but how this structure influences stimulus-evoked defensive responses and threat perception remains unclear. Here, we show that Crhr2-expressing neurons in mouse LS exhibit phasic activation upon detection of threatening but not rewarding stimuli. Threat-stimulus-driven activity predicts the probability but not vigor or type of defensive behavior evoked. Although necessary for and sufficient to potentiate stimulus-triggered defensive responses, LS neurons do not promote specific behaviors. Rather, their stimulation elicits negative valence and physiological arousal. Moreover, LS activity tracks brain state fluctuations and drives cortical activation and rapid awakening in the absence of threat. Together, our findings suggest that LS directs bottom-up modulation of cortical function to evoke preparatory defensive internal states and selectively enhance responsivity to threat-related stimuli.
突然的意外环境变化会引起注意，而当被视为潜在危险时，会引起防御性的行为状态。外侧隔核 (LS) 的干扰即使是无害的刺激也会产生极度的过度防御，但该结构如何影响刺激引起的防御反应和威胁感知仍不清楚。在这里，我们表明，在检测到威胁但不是奖励刺激时，小鼠 LS 中表达 Crhr2 的神经元会表现出相位激活。威胁刺激驱动的活动预测了防御行为的概率，但不能预测防御行为的活力或类型。尽管 LS 神经元对于增强刺激触发的防御反应是必要的和充分的，但它们并不促进特定的行为。相反，它们的刺激会引起负面的情绪和生理唤醒。此外，LS 的活动可以跟踪大脑状态的波动，并在没有威胁的情况下驱动皮层的激活和快速觉醒。总之，我们的研究结果表明，LS 指导着从下至上的皮层功能调制，以引起预备性的防御性内部状态，并选择性地增强对与威胁相关的刺激的反应性。
