Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine / Nanhu Brain-computer Interface Institute, Hangzhou, China.
Nat Neurosci. 2024 Mar;27(3):514-526. doi: 10.1038/s41593-023-01562-7. Epub 2024 Feb 12.
Fear-related disorders (for example, phobias and anxiety) cause a substantial public health problem. To date, studies of the neural basis of fear have mostly focused on the amygdala. Here we identify a molecularly defined amygdala-independent tetra-synaptic pathway for olfaction-evoked innate fear and anxiety in male mice. This pathway starts with inputs from the olfactory bulb mitral and tufted cells to pyramidal neurons in the dorsal peduncular cortex that in turn connect to cholecystokinin-expressing (Cck) neurons in the superior part of lateral parabrachial nucleus, which project to tachykinin 1-expressing (Tac1) neurons in the parasubthalamic nucleus. Notably, the identified pathway is specifically involved in odor-driven innate fear. Selective activation of this pathway induces innate fear, while its inhibition suppresses odor-driven innate fear. In addition, the pathway is both necessary and sufficient for stress-induced anxiety-like behaviors. These findings reveal a forebrain-to-hindbrain neural substrate for sensory-triggered fear and anxiety that bypasses the amygdala.
与恐惧相关的障碍（例如恐惧症和焦虑症）会导致严重的公共卫生问题。迄今为止，对恐惧的神经基础的研究大多集中在杏仁核上。在这里，我们确定了一种分子定义的、与杏仁核无关的四突触通路，用于雄性小鼠嗅觉诱发的先天恐惧和焦虑。这条通路始于嗅球僧帽细胞和丛状细胞向背侧脚间皮质的锥体神经元的输入，这些神经元反过来又与外侧臂旁核上部表达胆囊收缩素（Cck）的神经元相连，后者投射到副下丘脑核中表达速激肽 1（Tac1）的神经元。值得注意的是，所确定的途径专门涉及气味驱动的先天恐惧。这条通路的选择性激活会引起先天恐惧，而其抑制会抑制气味驱动的先天恐惧。此外，该通路是应激诱导的焦虑样行为所必需且充分的。这些发现揭示了一种绕过杏仁核的感觉触发的恐惧和焦虑的大脑前脑-后脑神经基质。
