Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes

Jeffrey Stedehouder, Bradley M. Roberts, Shinil Raina, Simon Bossi, Alan King Lun Liu, Natalie M. Doig, Kevin McGerty, Peter J. Magill, Laura Parkkinen and Stephanie J. Cragg ()
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Jeffrey Stedehouder: University of Oxford
Bradley M. Roberts: University of Oxford
Shinil Raina: University of Oxford
Simon Bossi: University of Oxford
Alan King Lun Liu: University of Oxford
Natalie M. Doig: Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network
Kevin McGerty: University of Oxford
Peter J. Magill: University of Oxford
Laura Parkkinen: University of Oxford
Stephanie J. Cragg: University of Oxford

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a “soma-to-soma” satellite-like configuration not typically observed for other striatal neurons. We find that transient depolarization of astrocytes in mouse striatum reversibly regulates ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.

Date: 2024
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DOI: 10.1038/s41467-024-54253-7

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