Top-down control of flight by a non-canonical cortico-amygdala pathway

• 成果类型: Article
• 署名作者: Borkar, Chandrashekhar D.; Stelly, Claire E.; Fu, Xin; Dorofeikova, Maria; Le, Quan-Son Eric; Vutukuri, Rithvik; Vo, Catherine; Walker, Alex; Basavanhalli, Samhita; Duong, Anh; Bean, Erin; Resendez, Alexis; Parker, Jones G.; Tasker, Jeffrey G.; Fadok, Jonathan P.
• 署名单位: Tulane University; Tulane University; Loyola University New Orleans; Tulane University; Northwestern University; Feinberg School of Medicine; Tulane University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6199
• DOI: 10.1038/s41586-023-06912-w
• 发表日期: 2024-01-25
• 关键词: fear; circuits; ORGANIZATION; connectivity; PERSPECTIVES; responses; selection; BEHAVIOR; neurons

摘要

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 disorder1. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA)2; 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. This study describes a projection from the medial prefrontal cortex to the central amygdala that is involved in the regulation of defensive responses to threat.