Dual metabotropic glutamate receptor signaling enables coordination of astrocyte and neuron activity in developing sensory domains

Astrocytes play an essential role in the development of neural circuits by positioning transporters and receptors near synapses and secreting factors that promote synaptic maturation. However, the mechanisms that coordinate astrocyte and neural maturation remain poorly understood. Using in vivo imaging in unanesthetized neonatal mice, we show that bursts of neuronal activity passing through nascent sound processing networks reliably induce calcium transients in astrocytes. Astrocyte transients were dependent on intense neuronal activity and constrained to regions near active synapses, ensuring close spatial and temporal coordination of neuron and astrocyte activity. Astrocyte responses were restricted to the pre-hearing period and induced by synergistic activation of two metabotropic glutamate receptors, mGluR5 and mGluR3, which promoted IP3R2-dependent calcium release from intracellular stores. The widespread expression of these receptors by astrocytes during development and the prominence of neuronal burst firing in emerging neural networks may help coordinate the maturation of excitatory synapses. [Display omitted] •Astrocytes and neurons exhibit coordinated activity in developing sensory domains•Only robust neuronal events lead to activation of nearby astrocytes•Large-scale coordinated astrocyte-neuron activity is limited to early development•Astrocyte calcium events are induced by synergistic activation of mGluR5 and mGluR3 Kellner et al. show that neuronal burst firing in developing central auditory centers triggers calcium increases in nearby astrocytes. This coordinated activity requires synergistic activation of mGluR5 and mGluR3 in astrocytes and disappears after hearing onset, suggesting that it may help promote maturation of sound processing circuits in the brain.