Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning.

Autor:	Hösli L; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Binini N; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Ferrari KD; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Thieren L; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Looser ZJ; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Zuend M; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Zanker HS; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Berry S; Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland., Holub M; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland., Möbius W; Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany., Ruhwedel T; Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany., Nave KA; Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany., Giaume C; Center for Interdisciplinary Research in Biology (CIRB), Collège de France, 75231 Paris Cedex 05, France., Weber B; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland. Electronic address: bweber@pharma.uzh.ch., Saab AS; Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, 8057 Zurich, Switzerland. Electronic address: asaab@pharma.uzh.ch.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Mar 08; Vol. 38 (10), pp. 110484.
DOI:	10.1016/j.celrep.2022.110484
Abstrakt:	The mechanisms by which astrocytes modulate neural homeostasis, synaptic plasticity, and memory are still poorly explored. Astrocytes form large intercellular networks by gap junction coupling, mainly composed of two gap junction channel proteins, connexin 30 (Cx30) and connexin 43 (Cx43). To circumvent developmental perturbations and to test whether astrocytic gap junction coupling is required for hippocampal neural circuit function and behavior, we generate and study inducible, astrocyte-specific Cx30 and Cx43 double knockouts. Surprisingly, disrupting astrocytic coupling in adult mice results in broad activation of astrocytes and microglia, without obvious signs of pathology. We show that hippocampal CA1 neuron excitability, excitatory synaptic transmission, and long-term potentiation are significantly affected. Moreover, behavioral inspection reveals deficits in sensorimotor performance and a complete lack of spatial learning and memory. Together, our findings establish that astrocytic connexins and an intact astroglial network in the adult brain are vital for neural homeostasis, plasticity, and spatial cognition. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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