Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes

Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+ is voltage dependent, but astrocyte membrane potential (V-m) is thought to be largely invariant. As a result, these voltage dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators to enable the measurement of V-m at peripheral astrocyte processes (PAPs) in mice, we report large, rapid, focal and pathway-specific depolarizations in PAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic glutamate transporters. We find that PAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of subcellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction. Using voltage imaging, Armbruster et al. show that neuronal activity induces large, rapid and synapse-specific astrocyte depolarizations that enhance synaptic glutamate signaling, representing a novel form of neuron-astrocyte communication.

Automated summary

This study reveals a novel form of communication between astrocytes and neurons, where neuronal activity induces significant depolarizations in astrocyte processes. These depolarizations are driven by presynaptic potassium efflux and glutamate transporters, and they inhibit astrocyte glutamate clearance, enhancing neuronal activation by glutamate.