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Neurovascular coupling in the basolateral amygdala modulates negative emotions

Jiayu Ruan^1,2,3,4 , Xinghua Quan³ , Huiqi Xie³ , Yiyi Zhang³ , Dongdong Zhang² , Wentao Wang³ , Bingrui Zhao³ , Danping Lu² , Yuxiao Niu⁵ , Jie-Min Jia^2,3,4,6,*

¹College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China
²Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
³Laboratory of Neurovascular Biology, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
⁴Laboratory of Neurovascular Biology, Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
⁵Laboratory of Computational and Functional Genomics, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
⁶State Key Laboratory of Gene Expression, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
* Correspondence: Jie-Min Jia(jiajiemin@westlake.edu.cn)

Emotion induces changes in regional cerebral blood flow, a manifestation of neurovascular coupling (NVC). However, whether NVC provides feedback to actively modulate emotion remains unexplored. Here, we demonstrate that NVC actively and bidirectionally modulates stress-induced negative emotions. We established bidirectional manipulations of NVC in freely moving mice by employing integrated pharmacological, genetic, and arteriolar optogenetic approaches. Our results showed that both systemic and region-specific NVC deficiencies in the basolateral amygdala (BLA) heightened emotional responses when mice transitioned from a safe, familiar environment to anxiogenic environments and that local restoration of NVC in the BLA normalized these responses. Mechanistically, NVC dysfunction impaired the capacity of BLA neuronal scaling during state transitions, manifesting as a characteristic biphasic pattern of c-Fos topology. NVC-deficient animals aberrantly adopted high-stress configurations under mild stress but regressed to low-stress templates during high-demand survival threats, thereby compromising defensive sustainability. Notably, the genetic NVC-enhancement model counteracted NVC impairments caused by chronic stress, thereby alleviating stress-driven emotional distress. These findings establish NVC in the BLA as an allostatic program that fine-tunes neural circuit activity during emotional responses, with implications for understanding and treating emotional disorders.

https://doi.org/10.1038/s41422-026-01256-2

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