Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, 330031, Nanchang, China.
Department of Biological Science, School of Life Science, Nanchang University, 330031, Nanchang, China.
Nat Commun. 2020 May 6;11(1):2221. doi: 10.1038/s41467-020-15920-7.
Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.
前额叶对杏仁核的控制失调与包括抑郁和焦虑障碍在内的精神疾病的发病机制有关。在这里，我们表明，在慢性束缚应激（CRS）诱导的啮齿动物焦虑模型中，这种失调发生在接受来自背内侧前额叶皮层（dmPFC→BLA PNs）单向输入的基底外侧杏仁核投射神经元中，而不是与 dmPFC 相互连接的那些神经元中（dmPFC↔BLA PNs）。具体来说，CRS 会使 dmPFC 驱动的兴奋性-抑制性平衡向前者的兴奋方向倾斜，但不会向后者倾斜。这种特异性优先于 dmPFC 建立的连接，这是由于突触前谷氨酸释放增强所致，并且与应激小鼠的焦虑样行为增加高度相关。重要的是，BLA 中 dmPFC 传入的低频光遗传学刺激可使增强的前额叶谷氨酸释放到 dmPFC→BLA PNs 正常化，并持久减弱 CRS 诱导的焦虑样行为增加。因此，我们的研究结果揭示了基于靶细胞的 mPFC 到杏仁核传递失调是应激诱导焦虑的原因。
