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

ABSTRACT

Astrocytes are increasingly thought 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. Transient depolarization of astrocytes in mouse striatum reversibly regulated 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.

FILE DESCRIPTIONS

This repository contains the following files:

• Key Resources Table (.xlsx) - Table containing details on key resources (antibodies, mouse lines, virus strains, software, equipment, and reagents), and the persistent identifiers for protocols and code used and generated in this study. 
• Source Data Folder (.zip):
  • _README_Source_Data (.txt) with detailed information about each dataset.
  • Individual tabular datasets corresponding to each panel shown in the Main Figures 1 to 5 (.csv).
  • Excel spreadsheet containing all tabular datasets plotted in Main Figures 1 to 5 (.xlsx)
• Supplementary Data Folder (.zip):
  • _README_Supplementary_Data (.txt) with detailed information about each dataset.
  • Individual tabular datasets corresponding to each panel shown in the Supplementary Figures 1-9, 11-14 (.csv).
  • Excel spreadsheet containing all tabular datasets plotted in Supplementary Figures 1-9, 11-14 (.xlsx)