BACKGROUND The prefrontal cortex plays a critical role in regulating emotional behaviors, and dysfunction of prefrontal cortex-dependent networks has been broadly implicated in mediating stress-induced behavioral disorders including major depressive disorder. METHODS Here we acquired multicircuit in vivo activity from eight cortical and limbic brain regions as mice were subjected to the tail suspension test (TST) and an open field test. We used a linear decoder to determine whether cellular responses across each of the cortical and limbic areas signal movement during the TST and open field test. We then performed repeat behavioral testing to identify which brain areas show cellular adaptations that signal the increase in immobility induced by repeat TST exposure. RESULTS The increase in immobility observed during repeat TST exposure is linked to a selective functional upregulation of cellular activity in infralimbic cortex and medial dorsal thalamus, and to an increase in the spatiotemporal dynamic interaction between these structures. Inducing this spatiotemporal dynamic using closed-loop optogenetic stimulation is sufficient to increase movement in the TST in stress-naive mice, while stimulating above the carrier frequency of this circuit suppressed movement. This demonstrates that the adaptations in infralimbic cortex-medial dorsal thalamus circuitry observed after stress reflect a compensatory mechanism whereby the brain drives neural systems to counterbalance stress effects. CONCLUSIONS Our findings provide evidence that targeting endogenous spatiotemporal dynamics is a potential therapeutic approach for treating stress-induced behavioral disorders, and that dynamics are a critical axis of manipulation for causal optogenetic studies.

中文翻译：

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皮质边缘回路的动态定时刺激激活压力补偿途径

背景前额叶皮层在调节情绪行为中起关键作用，前额叶皮层依赖网络的功能障碍广泛涉及介导压力诱发的行为障碍，包括重度抑郁症。方法 在这里，我们从八个皮质和边缘大脑区域获得了多回路体内活动，因为小鼠接受了悬尾试验 (TST) 和旷场试验。我们使用线性解码器来确定在 TST 和野外测试期间，每个皮层和边缘区域的细胞反应是否发出运动信号。然后，我们进行了重复行为测试，以确定哪些大脑区域显示出细胞适应性，表明重复 TST 暴露引起的不动性增加。结果 在重复 TST 暴露期间观察到的不动性增加与边缘下皮层和内侧背侧丘脑中细胞活性的选择性功能上调以及这些结构之间时空动态相互作用的增加有关。使用闭环光遗传学刺激诱导这种时空动态足以增加未应激小鼠 TST 的运动，同时在该电路的载波频率以上进行刺激抑制运动。这表明在压力后观察到的边缘下皮层内侧背侧丘脑回路中的适应性反映了一种补偿机制，即大脑驱动神经系统来平衡压力效应。