Breton, R. | bioRxiv Science

bioRxiv2024

Oxytocin Gαi signaling-induced amygdala astrocytes processes retraction shapes behavioral stress response

Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions are involved 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 Gi-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.

neuroscience↗

bioRxiv2020

Astrocytes close the critical period for visual plasticity

Summary paragraphBrain postnatal development is characterized by critical periods of experience-dependent remodeling1,2. Termination of these periods of intense plasticity is associated with settling of neuronal circuits, allowing for efficient information processing3. Failure to end critical periods thus results in neurodevelopmental disorders4,5. Yet, the cellular processes defining the timing of these developmental periods remain unclear. Here we show in the mouse visual cortex that astrocytes control the closure of the critical period. We uncover a novel underlying pathway involving regulation of the extracellular matrix that allows interneurons maturation via an unconventional astroglial connexin signaling. We find that timing of the critical period closure is controlled by a marked developmental upregulation of the astroglial protein connexin 30 that inhibits expression of the matrix degrading enzyme MMP9 through the RhoA-GTPase signaling pathway. Our results thus demonstrate that astrocytes not only influence activity and plasticity of single synapses, but are also key elements in the experience-dependent wiring of brain developing circuits. This work, by revealing that astrocytes promote the maturation of inhibitory circuits, hence provide a new cellular target to alleviate malfunctions associated to impaired closure of critical periods.

neuroscience↗