Fig. 1.

Astrocytes may dynamically control plasticity of mixed inhibitory and excitatory synapses. In the tightly wrapped synapse (left), Glu transporters facing the synapse can quickly take up released Glu, thereby preventing the activation of extrasynaptic Glu receptors. The simultaneous activation of synaptic GABA and Glu receptors results in balanced excitation and inhibition. During intense excitation, EAAT2 activity may also induce GABA release by reverse transport, thereby generating tonic inhibition [68, 69]. When astrocytic leaflets are withdrawn from the synapse (bottom), reduced Glu uptake leads to activation of presynaptic mGluRs inhibiting further Glu release and of extrasynaptic Glu receptors increasing tonic excitation. Asymmetric astrocytic coverage of axonal boutons and dendritic spines (right) [51] favors reduced Glu release by activating presynaptic mGluRs, resulting in a dominantly inhibitory response following GABA/Glu co-release