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Role of Astrocytes in critical periods

ABSTRACT: Brain postnatal development is characterized by critical periods of experience dependent remodeling. Maturation of local circuits inhibitory neurons terminate this period of enhanced plasticity. Astroglial cells are known to influence excitatory and inhibitory synaptic transmission as well as network activity through active signaling mechanisms. Although these can be developmentally regulated, the role of astrocytes in the timing of post-natal critical period is unknown. Here we show in the visual cortex that astrocytes con-trol the maturation of inhibitory neurons and thereby closure of the critical period. We uncover a novel underlying pathway involving regulation of the extracellular matrix that allows interneurons maturation via astroglial connexin signaling. We find that timing of the critical period closure is controlled by a marked upregulation of the astroglial protein connexin 30 that inhibits expression of the matrix degrading enzyme MMP9 through the RhoA-GTPase pathway. Our results thus demonstrate that astrocytes not only influ-ence neuronal activity but are also key elements in the experience–dependent wiring of brain circuits. Therefore, astrocytes represent a new cellular partner to consider in our understanding of the post-natal shaping of neuronal activities, hence providing a new target to alleviate malfunctions associated to im-paired closure of the critical period and settling of synaptic circuits.

INSTRUMENT(S): Q Exactive HF-X, Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Astrocyte Of The Cerebral Cortex

SUBMITTER: Valentin SABATET

LAB HEAD: Damarys Loew

PROVIDER: PXD020448 | Pride | 2022-05-12

REPOSITORIES: Pride

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			Action	DRS
	Design.xls	Xls
	ExtendeddataTable3-WFA.xls	Xls
	ExtendeddataTable4-Cx30.xls	Xls
	H2690FD.msf	Msf
	H2690FD.raw	Raw

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