journal article·2026-04Open access

Respiratory‐Limbic Coupling via a Thalamic Circuit Alleviates Anxiety

Shangyu Bi, Xiaoyi Wang, Huichun Luo, Ziteng Yue, Tianjiao Deng, Yuhang Liu, Xinxin Chen, Jianxu Zhao, Luo Shi, Ning Ma, Lingyan Mao, Jing Ding, Jiwen Xu, Ti‐Fei Yuan, Sheng Wang, Fang Yuan

Advanced Science· Volume 13· Issue 24

Abstract

ABSTRACT Breathing rhythms bidirectionally modulate affective states, yet the underlying neural pathways remain elusive. Here, we identified an ascending neural circuit that integrates respiratory patterning with affective state in male mice. This circuit originates from glutamatergic neurons in the preBötzinger complex (preBötC), projecting to the paraventricular thalamic nucleus (PVT) and subsequently targeting the central amygdala (CeA). We reveal that photostimulation of the preBötC→PVT circuit significantly alleviates acute restraint stress‐induced anxiety‐like phenotypes and reduces respiratory frequency variability. Conversely, inhibition of this circuit exacerbates anxiety‐like phenotypes and respiratory dysfunction. These effects are significantly abolished by inhibition or ablation of PVT neurons projecting to the CeA. Additionally, this anxiolytic effect is mediated by PVT projections that preferentially excite centrolateral amygdala neurons, thereby inhibiting centromedial amygdala output. Translating these findings, we show that volitional slow breathing reduces anxiety in healthy humans and suppresses anxiety‐related beta/high‐gamma oscillations in the amygdala of epilepsy patients. This work delineates a conserved respiratory‐limbic circuit that mechanistically explains the anxiolytic effect of controlled breathing.
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Research context

OpenAlex topics: Neuroscience of respiration and sleep · Sleep and Wakefulness Research · Vagus Nerve Stimulation Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Neurobiology Hebei Medical University Shijiazhuang China

Department of Anesthesiology, Renji Hospital, Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Neurology, Zhongshan Hospital Fudan University Shanghai China

Department of Neurosurgery Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Shanghai China

Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine and School of Psychology Shanghai China

Hebei Key Laboratory of Brain Science and Brain‐Inspired Intelligence Hebei Medical University Shijiazhuang China

The Key Laboratory of Neural and Vascular Biology Ministry of Education, Hebei Medical University Shijiazhuang China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Hebei Province · China Postdoctoral Science Foundation

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