Network-level encoding of local neurotransmitters in cortical astrocytes

Abstract

Astrocytes, the most abundant non-neuronal cell type in the mammalian brain, are crucial circuit components that respond to and modulate neuronal activity through calcium (Ca²⁺) signalling^1-7. Astrocyte Ca²⁺ activity is highly heterogeneous and occurs across multiple spatiotemporal scales-from fast, subcellular activity^3,4 to slow, synchronized activity across connected astrocyte networks^8-10-to influence many processes^5,7,11. However, the inputs that drive astrocyte network dynamics remain unclear. Here we used ex vivo and in vivo two-photon astrocyte imaging while mimicking neuronal neurotransmitter inputs at multiple spatiotemporal scales. We find that brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca²⁺ responses beyond an individual stimulated cell. Further, we find that a key subset of Ca²⁺ activity-propagative activity-differentiates astrocyte network responses to these two main neurotransmitters, and may influence responses to future inputs. Together, our results demonstrate that local, transient neurotransmitter inputs are encoded by broad cortical astrocyte networks over a minutes-long time course, contributing to accumulating evidence that substantial astrocyte-neuron communication occurs across slow, network-level spatiotemporal scales^12-14. These findings will enable future studies to investigate the link between specific astrocyte Ca²⁺ activity and specific functional outputs, which could build a consistent framework for astrocytic modulation of neuronal activity.