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PACAP-PAC1R signaling in the PSTh mediates stress-induced anxiety-like behavior in mice

GSE332821 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/07/20 Platform GPL24247
Summary
Stress represents a major risk factor for anxiety disorders, yet the underlying molecular substrates through which stress causes anxiety remain elusive. We employed an established stress paradigm to induce anxiety-like behaviors in mice and found that stress causes robust and sustained activation of glutamatergic neurons in the parasubthalamic nucleus (PSTh). Moreover, inhibition of those neurons significantly reduced anxiety-like behavior in stressed animals. RNA sequencing revealed that the pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1R, encoded by Adcyap1r1) is enriched in the PSTh. Ex vivo patch-clamp recordings showed that PACAP, an endogenous agonist of PAC1R, increases the excitability of PSTh neurons. Interestingly, pharmacological blockade of PAC1R within PSTh was sufficient to prevent anxiety by stress. These findings suggest that stress induces sustained activation of PSTh neurons PACAP-PAC1R signaling, ultimately leading to anxiety-like state.
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Also filed as BioProject PRJNA1469131 and SRA study SRP702704. Searching any of these in the dataset finder brings you back here.

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