Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, 90089, USA.
Graduate Program in Neuroscience, University of Southern California, Los Angeles, CA, 90089, USA.
Nat Commun. 2018 Mar 20;9(1):1151. doi: 10.1038/s41467-018-03581-6.
Zona incerta (ZI) is a functionally mysterious subthalamic nucleus containing mostly inhibitory neurons. Here, we discover that GABAergic neurons in the rostral sector of ZI (ZIr) directly innervate excitatory but not inhibitory neurons in the dorsolateral and ventrolateral compartments of periaqueductal gray (PAG), which can drive flight and freezing behaviors respectively. Optogenetic activation of ZIr neurons or their projections to PAG reduces both sound-induced innate flight response and conditioned freezing response, while optogenetic suppression of these neurons enhances these defensive behaviors, likely through a mechanism of gain modulation. ZIr activity progressively increases during extinction of conditioned freezing response, and suppressing ZIr activity impairs the expression of fear extinction. Furthermore, ZIr is innervated by the medial prefrontal cortex (mPFC), and silencing mPFC prevents the increase of ZIr activity during extinction and the expression of fear extinction. Together, our results suggest that ZIr is engaged in modulating defense behaviors.
不确定区（ZI）是一个功能神秘的底丘脑核，其中主要包含抑制性神经元。在这里，我们发现 ZI 前区（ZIr）的 GABA 能神经元直接支配中脑导水管周围灰质（PAG）背外侧和腹外侧隔室的兴奋性神经元，但不支配抑制性神经元，这些神经元分别可以驱动飞行和冻结行为。光遗传激活 ZIr 神经元或其投射到 PAG 的投射可以减少声音诱导的先天飞行反应和条件性冻结反应，而光遗传抑制这些神经元则增强了这些防御行为，可能是通过增益调节的机制。在条件性冻结反应的消退过程中，ZIr 的活动逐渐增加，而抑制 ZIr 的活动则损害了恐惧消退的表达。此外，ZIr 被内侧前额叶皮层（mPFC）支配，沉默 mPFC 可以防止在消退过程中 ZIr 活动的增加和恐惧消退的表达。综上所述，我们的研究结果表明，ZIr 参与调节防御行为。
