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<p>Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions results in&#xa0;stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin-dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology-dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.</p>

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Stress induces oxytocin-Gαi-dependent remodeling of astrocytes to shape neuronal response in the amygdala

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Angel Baudon,
  • Valentin Grelot,
  • Kai-Yi Wang,
  • Ferdinand Althammer,
  • Clémence Denis,
  • Pierre Riché-Piotaix,
  • Azmal Syed Ali,
  • Yudong Yan,
  • Fernando Castillo Díaz,
  • Francesca Piacentini,
  • Etienne Clauss Creusot,
  • Volodya Hovhannisyan,
  • Tim Schubert,
  • Annabel C. Kleinwaechter,
  • Eva M. Eisemann,
  • Jabir Aliyu Muhammad,
  • Jemima Helen,
  • Tom Lakomy,
  • Quirin Krabichler,
  • Rachel Breton,
  • Virginie Andry,
  • Maria-Angeles Carrillo-de Sauvage,
  • Valérie Demais,
  • Aurélia Cès,
  • Felix Franke,
  • Franziska Schommer,
  • Mélanie Kremer,
  • Barbara Di Benedetto,
  • Yannick Goumon,
  • Christian P. Schaaf,
  • Valery Grinevich,
  • Nathalie Rouach,
  • Pascal Darbon,
  • Inga D. Neumann,
  • Antoine Adamantidis,
  • Marta Busnelli,
  • Lucile Benhaim,
  • Jeroen Krijgsveld,
  • Frank W. Pfrieger,
  • Alexandre Charlet

摘要

Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions results in stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin-dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology-dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.