What does this research mean for the field?

Dysfunction in the coordinated regulation of opposing glutamatergic and GABAergic dmPFC-LHb pathways by ATP-P2X2R signaling mediates stress susceptibility, and restoring this excitatory/inhibitory balance promotes resilience. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to uncover the mechanisms by which chronic stress leads to emotional susceptibility or resilience in male mice.

June 29, 2026Nature CommunicationsOpen Access

A dual-pathway dysregulation in prefrontal-habenular circuits mediates stress susceptibility

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Authors

JWJijin Wu XTXiaohan Tong RSRuizhe Sun

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Overview

Randomized trial shows dual-pathway dysregulation affecting stress susceptibility in male mice, indicating potential therapeutic targets for depression.

Key Points

This research aims to uncover the mechanisms by which chronic stress leads to emotional susceptibility or resilience in male mice.
Identified dual-pathway mechanisms in the dorsomedial prefrontal cortex-lateral habenula circuit.
Conducted chemogenetic experiments to manipulate excitatory/inhibitory balance in mice subjected to chronic stress.
Analyzed effects of ATP-P2X2R signaling on GABAergic neuron function and stress response.
Chronic stress induced hyperactivity in LHb neurons through disrupted E/I balance via enhanced glutamatergic and reduced GABAergic inputs.
Chemogenetic recapitulation of E/I imbalance further exacerbated LHb hyperactivity and stress susceptibility.
Restoration of E/I balance promoted resilience in stressed mice.

Cite This Study

Wu et al. (2026) studied this question.

synapsesocial.com/papers/6a420a74f91bb43ea9191dba https://doi.org/10.1038/s41467-026-74754-x

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June 29, 2026Nature CommunicationsOpen Access

A dual-pathway dysregulation in prefrontal-habenular circuits mediates stress susceptibility

View Full Paper

Ask AI

Bookmark

Authors

JWJijin Wu XTXiaohan Tong RSRuizhe Sun

Discussion

Member takes

Overview

Randomized trial shows dual-pathway dysregulation affecting stress susceptibility in male mice, indicating potential therapeutic targets for depression.

Key Points

This research aims to uncover the mechanisms by which chronic stress leads to emotional susceptibility or resilience in male mice.
Identified dual-pathway mechanisms in the dorsomedial prefrontal cortex-lateral habenula circuit.
Conducted chemogenetic experiments to manipulate excitatory/inhibitory balance in mice subjected to chronic stress.
Analyzed effects of ATP-P2X2R signaling on GABAergic neuron function and stress response.
Chronic stress induced hyperactivity in LHb neurons through disrupted E/I balance via enhanced glutamatergic and reduced GABAergic inputs.
Chemogenetic recapitulation of E/I imbalance further exacerbated LHb hyperactivity and stress susceptibility.
Restoration of E/I balance promoted resilience in stressed mice.

Cite This Study

Wu et al. (2026) studied this question.

synapsesocial.com/papers/6a420a74f91bb43ea9191dba https://doi.org/10.1038/s41467-026-74754-x

View Full Paper

Ask AI

Bookmark