Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 20, Pages 8467-8472Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1016650108
Keywords
hippocampus; neuroglial interactions
Categories
Funding
- Human Frontier Science Program Organization
- Agence Nationale de la Recherche
- Institut National de la Sante et de la Recherche Medicale
- French Research Ministry
- Deutsche Forschungsgemeinschaft
- Franco Czech Barrande Program (Hubert Curien Program)
- Grant Agency of the Czech Republic [309/09/1597]
- Academy of Sciences of the Czech Republic [AVOZ50390512]
- Ministry of Education, Youth and Sports of the Czech Republic [1M0538]
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Astrocytes dynamically interact with neurons to regulate synaptic transmission. Although the gap junction proteins connexin 30 (Cx30) and connexin 43 (Cx43) mediate the extensive network organization of astrocytes, their role in synaptic physiology is unknown. Here we show, by inactivating Cx30 and Cx43 genes, that astroglial networks tone down hippocampal synaptic transmission in CA1 pyramidal neurons. Gap junctional networking facilitates extracellular glutamate and potassium removal during synaptic activity through modulation of astroglial clearance rate and extracellular space volume. This regulation limits neuronal excitability, release probability, and insertion of postsynaptic AMPA receptors, silencing synapses. By controlling synaptic strength, connexins play an important role in synaptic plasticity. Altogether, these results establish connexins as critical proteins for extracellular homeostasis, important for the formation of functional synapses.
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