Top-down control of flight by a non-canonical cortico-amygdala pathway.
Top-down control of flight by a non-canonical cortico-amygdala pathway.
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DOI：
10.1038/s41586-023-06912-w
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发表时间：
2024-01
期刊：
影响因子：
64.8
通讯作者：
C. Borkar;Claire E. Stelly;Xin Fu;Maria Dorofeikova;Quan-Son Eric Le;Rithvik Vutukuri;Catherine Vo;Alex Walker;S. Basavanhalli;A. Duong;E. Bean;A. Resendez;Jones G Parker;Jeffrey G. Tasker;J. Fadok
中科院分区：
文献类型：
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作者：
C. Borkar;Claire E. Stelly;Xin Fu;Maria Dorofeikova;Quan-Son Eric Le;Rithvik Vutukuri;Catherine Vo;Alex Walker;S. Basavanhalli;A. Duong;E. Bean;A. Resendez;Jones G Parker;Jeffrey G. Tasker;J. Fadok
生存需要选择适当的行为来应对威胁，而失调的防御反应与创伤后应激障碍和恐慌症等精神疾病有关。威胁诱发的行为，包括冻结和逃跑，是由中央杏仁核（CeA）的神经元回路控制的；然而，导致高强度防御反应的CeA神经元兴奋的来源尚不清楚。在这里，我们结合了神经解剖制图、体内钙成像、功能操作和电生理学来表征从背脚（DP）前额叶皮层到CeA的未知投影。DP-to-CeA神经元是谷氨酸能神经元，专门针对内侧CeA，这是杏仁核的主要输出核，介导对威胁的条件反应。使用一种引发条件冻结和逃跑的行为范式，我们发现cea -投射DP神经元被高强度威胁以情境依赖的方式激活。功能操作表明，DP-to-CeA通路对于回避行为和飞行都是必要和充分的。此外，我们发现DP神经元与投射到中脑飞行中心的内侧CeA内的神经元突触。这些结果阐明了一个非规范的自上而下的途径调节防御反应。
Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA); however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.