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+) signalling1–7 . Astrocyte Ca2+ activity is highly heterogeneous and occurs across multiple spatiotemporal scales—from fast, subcellular activity3,4 to slow, synchronized activity across connected astrocyte networks8–10—to infuence many processes5,7,11. 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 fnd that brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca2+ responses beyond an individual stimulated cell. Further, we fnd that a key subset of Ca2+ activity—propagative activity—diferentiates astrocyte network responses to these two main neurotransmitters, and may infuence 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 scales12–14. These fndings will enable future studies to investigate the link between specifc astrocyte Ca2+ activity and specifc functional outputs, which could build a consistent framework for astrocytic modulation of neuronal activity.