Astrocytic strengthening of synaptic plasticity via non-vesicular and channel-mediated glutamate release

Abstract

Recent studies have revealed a novel role for astrocytes in the neuronal synaptic plasticity as they can release excitatory amino acids (EAAs) such as glutamate that activate neuronal NMDA receptors. Vesicular and non-vesicular mechanisms have been suggested for controlling astrocytic glutamate release, but exact molecular correlates are unclear. Here we report that mouse astrocytes express functional Ca²⁺-activated anion channels (CAACs), which are readily activated by increases in intracellular Ca²⁺ by various astrocytic G_q-coupled receptors, and encoded by mouse bestrophin 1 (mBest1) channel. mBest1 provides a molecular mechanism for Ca²⁺-dependent non-vesicular and channel-mediated glutamate release from astrocytes. Furthermore, glutamate release through mBest1 induces the potentiation of hippocampal CA3-CA1 synaptic activity by modulating the threshold of synaptic plasticity. Our results both provide a novel mechanism of gliotransmitter release by direct permeation through astrocytic CAACs and suggest a potential role in regulating hippocampal synaptic plasticity by modulation of neuronal NMDA receptors. [J Physiol Sci. 2008;58 Suppl:S11]