Details

Autor(en) / Beteiligte

• Flora Vasile
• Elena Dossi
• Julien Moulard
• Pascal Ezan
• Laure Lecoin
• Martine Cohen-Salmon
• Philippe Mailly
• Marc Le Bert
• Isabelle Couillin
• Alexis Bemelmans
• Nathalie Rouach

Titel

Pannexin 1 activity in astroglia sets hippocampal neuronal network patterns

Ist Teil von

• PLoS biology, 2022-12, Vol.20 (12)

Ort / Verlag

Public Library of Science (PLoS)

Erscheinungsjahr

2022

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Astroglial release of molecules is thought to actively modulate neuronal activity, but the nature, release pathway, and cellular targets of these neuroactive molecules are still unclear. Pannexin 1, expressed by neurons and astrocytes, form nonselective large pore channels that mediate extracellular exchange of molecules. The functional relevance of these channels has been mostly studied in brain tissues, without considering their specific role in different cell types, or in neurons. Thus, our knowledge of astroglial pannexin 1 regulation and its control of neuronal activity remains very limited, largely due to the lack of tools targeting these channels in a cell-specific way. We here show that astroglial pannexin 1 expression in mice is developmentally regulated and that its activation is activity-dependent. Using astrocyte-specific molecular tools, we found that astroglial-specific pannexin 1 channel activation, in contrast to pannexin 1 activation in all cell types, selectively and negatively regulates hippocampal networks, with their disruption inducing a drastic switch from bursts to paroxysmal activity. This decrease in neuronal excitability occurs via an unconventional astroglial mechanism whereby pannexin 1 channel activity drives purinergic signaling-mediated regulation of hyperpolarisation-activated cyclic nucleotide (HCN)-gated channels. Our findings suggest that astroglial pannexin 1 channel activation serves as a negative feedback mechanism crucial for the inhibition of hippocampal neuronal networks. Astrocytes have mostly been shown to boost neuronal activity. This study reveals that activity-dependent activation of astroglial pannexin 1 channels inhibits hippocampal neuronal networks by decreasing neuronal excitability via purinergic signaling, uncovering a novel astroglial negative feedback loop mechanism.