Upregulation of astroglial connexin 30 impairs hippocampal synaptic activity and recognition memory.

Eléonore Hardy, Julien Moulard, Augustin Walter, Pascal Ezan, Alexis-Pierre Bemelmans, Franck Mouthon, Mathieu Charvériat, Nathalie Rouach, Armelle Rancillac

PLoS biology 2023 Apr

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Astrocytes crucially contribute to synaptic physiology and information processing. One of their key characteristics is to express high levels of connexins (Cxs), the gap junction-forming protein. Among them, Cx30 displays specific properties since it is postnatally expressed and dynamically upregulated by neuronal activity and modulates cognitive processes by shaping synaptic and network activities, as recently shown in knockout mice. However, it remains unknown whether local and selective upregulation of Cx30 in postnatal astrocytes within a physiological range modulates neuronal activities in the hippocampus. We here show in mice that, whereas Cx30 upregulation increases the connectivity of astroglial networks, it decreases spontaneous and evoked synaptic transmission. This effect results from a reduced neuronal excitability and translates into an alteration in the induction of synaptic plasticity and an in vivo impairment in learning processes. Altogether, these results suggest that astroglial networks have a physiologically optimized size to appropriately regulate neuronal functions. Copyright: © 2023 Hardy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Eléonore Hardy, Julien Moulard, Augustin Walter, Pascal Ezan, Alexis-Pierre Bemelmans, Franck Mouthon, Mathieu Charvériat, Nathalie Rouach, Armelle Rancillac. Upregulation of astroglial connexin 30 impairs hippocampal synaptic activity and recognition memory. PLoS biology. 2023 Apr;21(4):e3002075