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Feedforward inhibition of stress by brainstem neuropeptide Y neurons.

ABSTRACT: Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initiating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously uncharacterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice. NPY^DRN/vlPAG neurons are rapidly activated by various stressful stimuli. Inhibiting these neurons exacerbated hypophagic and anxiety responses during stress, while activation significantly ameliorates acute stress-induced hypophagia and anxiety levels and transmits positive valence. Furthermore, NPY^DRN/vlPAG neurons exert differential but synergic anxiolytic effects via inhibitory projections to the paraventricular thalamic nucleus (PVT) and the lateral hypothalamic area (LH). Together, our findings reveal a feedforward inhibition neural mechanism underlying stress resistance and suggest NPY^DRN/vlPAG neurons as a potential therapeutic target for stress-related disorders.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC11365948 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Feedforward inhibition of stress by brainstem neuropeptide Y neurons.

Zhang Yan Y Shen Jiayi J Xie Famin F Liu Zhiwei Z Yin Fangfang F Cheng Mingxiu M Wang Liang L Cai Meiting M Herzog Herbert H Wu Ping P Zhang Zhi Z Zhan Cheng C Liu Tiemin T

Nature communications 20240901 1

Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initiating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously uncharacterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice. NPY<sup>DRN/v ...[more]

PMID: 39217143

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Feedforward inhibition of stress by brainstem neuropeptide Y neurons.

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Feedforward inhibition of stress by brainstem neuropeptide Y neurons.

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