Volume transmission signalling via astrocytes

Abstract

The influence of astrocytes on synaptic function has been increasingly studied, owing to the discovery of both gliotransmission and morphological ensheathment of synapses. While astrocytes exhibit at best modest membrane potential fluctuations, activation of G-protein coupled receptors (GPCRs) leads to a prominent elevation of intracellular calcium which has been reported to correlate with gliotransmission. In this review, the possible role of astrocytic GPCR activation is discussed as a trigger to promote synaptic plasticity, by affecting synaptic receptors through gliotransmitters. Moreover, we suggest that volume transmission of neuromodulators could be a biological mechanism to activate astrocytic GPCRs and thereby to switch synaptic networks to the plastic mode during states of attention in cerebral cortical structures.

Keywords: Gq signalling; IP3 receptors; acetylcholine; d-serine; gamma oscillations.

Figure 1.

Wiring transmission versus volume transmission and their effects on astrocytes. (a) Wiring transmission targets designated synapses and produces localized responses in perisynaptic astrocytic processes. (b) In volume transmission, the neuromodulators diffuse into tortuous and convoluted ECS upon release from en passant varicosities. Such ECS diffusion results in activation of astrocytic GPCRs in larger areas than a synaptic component, resulting in synchronized and spatially spread astrocytic Ca²⁺ activities. (c) Volume transmission and synaptic transmission can occur simultaneously in brain states characterized by neuromodulator release, for instance, during attention.

Figure 2.

Schematic diagram for neuron–astrocyte interaction in the context of gamma-state-induced synaptic plasticity. Attentive states drive volume transmission of subcortical neuromodulators which in turn activates neuronal gamma oscillations and astrocytic gliotransmission to establish a state for synaptic plasticity induction. Sensory and social experience enhances neuromodulator production and gliotransmission of cytokines enhances gamma oscillations, although the exact mechanism remains to be elucidated. ACh, acetylcholine; NA, noradrenaline; E, excitatory neuron; I, inhibitory neuron.