Network-level encoding of local neurotransmitters in cortical astrocytes

CAHILL, MICHELLE K.; COLLARD, MAX; TSE, VINCENT; REITMAN, MICHAEL E.; ETCHENIQUE, ROBERTO; KIRST, CHRISTOPH; POSKANZER, KIRA E.

NATURE

NATURE PUBLISHING GROUP

Año: 2024

0028-0836

Astrocytes, the most abundant non-neuronal cell type in the mammalian brain, arecrucial circuit components that respond to and modulate neuronal activity throughcalcium (Ca2+) signalling1–7. Astrocyte Ca2+ activity is highly heterogeneous and occursacross multiple spatiotemporal scales—from fast, subcellular activity3,4 to slow, synchronized activity across connected astrocyte networks8–10—to infuence manyprocesses5,7,11. However, the inputs that drive astrocyte network dynamics remainunclear. Here we used ex vivo and in vivo two-photon astrocyte imaging whilemimicking 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—diferentiatesastrocyte network responses to these two main neurotransmitters, and may infuenceresponses to future inputs. Together, our results demonstrate that local, transientneurotransmitter inputs are encoded by broad cortical astrocyte networks over aminutes-long time course, contributing to accumulating evidence that substantialastrocyte–neuron communication occurs across slow, network-level spatiotemporalscales12–14. These fndings will enable future studies to investigate the link betweenspecifc astrocyte Ca2+ activity and specifc functional outputs, which could build aconsistent framework for astrocytic modulation of neuronal activity.