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

PLoS Biol. 2023 Apr 11;21(4):e3002075. doi: 10.1371/journal.pbio.3002075. eCollection 2023 Apr.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes* / metabolism
  • Connexin 30 / metabolism
  • Connexin 43* / genetics
  • Connexin 43* / metabolism
  • Connexins / genetics
  • Connexins / metabolism
  • Hippocampus / metabolism
  • Mice
  • Mice, Knockout
  • Up-Regulation

Substances

  • Connexin 30
  • Connexin 43
  • Connexins

Grants and funding

This work was supported by an industrial convention for training through research (CIFRE) provided by the Association National de la Recherché Technologie (ANRT) for E.H. and grants from the European Research Council (Consolidator grant #683154), Centre National de la Recherche Scientifique (CNRS), the French Institute of Health and Medical Research (Inserm), Bettencourt Schueller Foundation and the Collège de France to N.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.