A delayed activation of multiple neurons (right, bottom) is due to astrocyte glutamate release.


Astroctyes are known to modulate synaptic communication between neurons. Now, Olivier Pascual (University of Pennsylvania, Philadelphia, PA), Tommaso Fellin, Giorgio Carmignoto (University of Padova, Italy), and colleagues report that astrocytes can elicit slow inward currents outside of synapses and thus activate synchronous responses in multiple neurons.

During periods of intense neural activity, calcium oscillations are triggered in astrocytes, inducing the cells to release glutamate. Fellin et al. find that this glutamate release stimulates neuronal activity in hippocampal slices. Photolysis of caged Ca2+ in single astrocytes almost exclusively activates the extrasynaptic NMDA receptors in CA1 pyramidal neurons. Thus, the astrocytes are triggering neural activity by turning on receptors outside of the synaptic junction itself—receptors that are abundant but whose role has been unknown.

Based on electrical activity and fluorescent probes, the team also found that astrocytes induce synchronous responses in multiple neurons. Although they can't yet say whether a single astrocyte is able to activate multiple neurons, they hypothesize that one glutamate release event may be sufficient to reach the dendrites of several neurons.

“Synchrony is central to information processing,” Carmignoto says. And because the astrocytes only release glutamate when the surrounding neural activity is high, their activation of several neurons at once may be important in memory formation or long-term potentiation. The coordinated activity also hints that the astrocytes may be involved in the pathophysiology that underlies epilepsy, which is characterized by coordinated waves of hyperactive neurons. ▪


Fellin, T., et al.