Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.


Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
11 04 2023
Historique:
received: 17 02 2023
revised: 01 04 2023
accepted: 03 04 2023
medline: 17 5 2023
pubmed: 16 5 2023
entrez: 16 5 2023
Statut: epublish

Résumé

Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic astroglial processes and plays major roles in synaptic transmission. We have previously found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain physiological synaptic transmissions and cognitiogns. However, whether Cx43 is important for the release of synaptic vesicles, which is a critical component of synaptic efficacy, remains unanswered. Here, using transgenic mice with a glial conditional knockout of Cx43 (Cx43-/-), we investigate whether and how astrocytes regulate the release of synaptic vesicles from hippocampal synapses. We report that CA1 pyramidal neurons and their synapses develop normally in the absence of astroglial Cx43. However, a significant impairment in synaptic vesicle distribution and release dynamics were observed. In particular, the FM1-43 assays performed using two-photon live imaging and combined with multi-electrode array stimulation in acute hippocampal slices, revealed a slower rate of synaptic vesicle release in Cx43-/- mice. Furthermore, paired-pulse recordings showed that synaptic vesicle release probability was also reduced and is dependent on glutamine supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for Cx43 in regulating presynaptic functions by controlling the rate and probability of synaptic vesicle release. Our findings further highlight the significance of astroglial Cx43 in synaptic transmission and efficacy.

Identifiants

pubmed: 37190042
pii: cells12081133
doi: 10.3390/cells12081133
pmc: PMC10136730
pii:
doi:

Substances chimiques

Connexin 43 0
Glutamine 0RH81L854J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Déclaration de conflit d'intérêts

The authors declare no conflicts of interest.

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Auteurs

Giselle Cheung (G)

Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, 75231 Paris, France.

Oana Chever (O)

Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, 75231 Paris, France.

Astrid Rollenhagen (A)

Institute for Neuroscience and Medicine INM-10, Research Center Jülich, 52428 Jülich, Germany.
Jülich-Aachen Research Alliance Translational Brain Medicine, 52056 Aachen, Germany.

Nicole Quenech'du (N)

Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, 75231 Paris, France.

Pascal Ezan (P)

Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, 75231 Paris, France.

Joachim H R Lübke (JHR)

Institute for Neuroscience and Medicine INM-10, Research Center Jülich, 52428 Jülich, Germany.
Jülich-Aachen Research Alliance Translational Brain Medicine, 52056 Aachen, Germany.
Department of Psychiatry, Psychotherapy and Psychosomatics, Rheinisch-Westfaelische Technische Hochschule Aachen University, 52056 Aachen, Germany.

Nathalie Rouach (N)

Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Labex Memolife, Université PSL, 75231 Paris, France.

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Classifications MeSH