Network-level encoding of local neurotransmitters in cortical astrocytes

Astrocytes, the most abundant non-neuronal cell type in the mammalian
brain, are crucial circuit components that respond to and modulate
neuronal activity via calcium (Ca2+) signaling. Astrocyte Ca2+ activity is
highly heterogeneous and occurs across multiple spatiotemporal scales—from
fast, subcellular activity to slow, synchronized activity across connected
astrocyte networks—to influence many processes. 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 major
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 significant
astrocyte-neuron communication occurs across slow, network-level
spatiotemporal scales. These findings will enable future studies
investigating the link between specific astrocyte Ca2+ activity and
specific functional outputs, which could build a consistent framework for
astrocytic modulation of neuronal activity.