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  Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning

Hösli, L., Binini, N., Ferrari, K. D., Thieren, L., Looser, Z. J., Zuend, M., et al. (2022). Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning. Cell Reports, 38(10): 110484. doi:10.1016/j.celrep.2022.110484.

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Hösli, L., Author
Binini, N., Author
Ferrari, K. D., Author
Thieren, L., Author
Looser, Z. J., Author
Zuend, M., Author
Zanker, H. S., Author
Berry, S., Author
Holub, M., Author
Möbius, W.1, Author              
Ruhwedel, T.1, Author              
Nave, K.-A.1, Author              
Giaume, C., Author
Weber, B., Author
Saab, A. S., Author
Affiliations:
1Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350301              

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Free keywords: CA1 synaptic plasticity; astrocytes; astrocytic network; connexin 30; connexin 43; gap junction coupling; hippocampus; spatial learning and memory.
 Abstract: 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 knock- outs. 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.

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Language(s): eng - English
 Dates: 2022-03-08
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.celrep.2022.110484
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Title: Cell Reports
Source Genre: Journal
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Pages: 18 Volume / Issue: 38 (10) Sequence Number: 110484 Start / End Page: - Identifier: -