Abstract Astrocytes close the critical period for visual plasticity

Brain postnatal development is characterized by critical periods of experience-dependent remodeling. Termination of this period of intense plasticity is associated with settling of neuronal circuits, allowing for efficient information processing. Failure to end critical periods thus results in neurodevelopmental disorders. Yet, the cellular processes defining the timing of this developmental period remain unclear. Here we show in the 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.

Short Biography

Glenn Dallérac performed his PhD and first postdoctoral work on neuronal activity and synaptic plasticity in physiological contexts as well as in the diseased brain. He notably described neuronal correlates of the brain ability to estimate time passing by and uncovered defects in this function in animal models of Huntington’s disease. Because of the research advances challenging the neurocentric view of brain functions he then turned his research toward the study of neuro-glial interactions. Astroglial cells indeed not only bridge the gap between metabolic supplies by blood vessels and neurons, they also allow fine control of neurotransmission by providing appropriate signaling molecules and insulation through a tight enwrapping of synapses. The research of Glenn Dallérac contributed to the recognition that astroglia is essential to neuronal communication. Evidences for such role mainly concerned the synaptic level by identifying the neuro-active molecules being uptaken or released by astrocytes at synaptic or extrasynaptic sites. Glenn Dallérac is currently a CNRS researcher leading the team “Astrocytes & Cognition” at the Paris-Saclay Institute of Neurosciences (NeuroPSI). The team investigates whether and how astrocytes play an active role in information processing in physiological and pathological conditions. To do so, a multiscale approach has been adopted, in order to study neuro-glial interactions at the synaptic, network and behavioral level.

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