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

Roberts BM
Raina S
Bossi S
Liu AKL
McGerty K
Parkkinen L
Cragg SJ

Astrocytes are brain cells that support nerve cells. Here, we show that astrocytes can rapidly influence the activity of nerve cells called cholinergic interneurons. Astrocytes and cholinergic interneurons are closely positioned, allowing both to work together to control release of the chemical messenger dopamine. These discoveries reveal a powerful form of astrocyte-nerve cell communication.

Scientific 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.

Microscope image of a human cholinergic interneuron with a 'satellite' astrocyte.
Example of a human cholinergic interneuron (red) with a 'satellite' astrocyte (green). The nuclei of cells are labelled in blue.
Citation

2024. Nat Commun, 15(1):10017.

DOI
10.1038/s41467-024-54253-7
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