Synaptic environment and extrasynaptic glutamate signals: The quest continues

Rusakov, Dmitri A. and Stewart, Michael G. (2021). Synaptic environment and extrasynaptic glutamate signals: The quest continues. Neuropharmacology, 195, article no. 108688.

DOI: https://doi.org/10.1016/j.neuropharm.2021.108688

Abstract

Glutamatergic synapses are excitatory synapses which play a key role in behaviour. Their intricate structure and content can only be fully appreciated from 3D reconstruction methods. Most important is the relationship between astroglia and glutamate synapses which plays a crucial role in the various aspects involved in release and diffusion, which are examined in this review. We consider the receptor actions of glutamate, inside and outside the synaptic cleft in the brain, where the organisation and micro-physiology of excitatory synapses and their environment could control glutamate escape. In what conditions and how far glutamate can escape the synaptic cleft activating its target receptors outside the immediate synapse has long been the subject of debate. Astroglia-dependent glutamate spillover is likely to be important across the spectrum of cognitive functions since it can be controlled by the induction of the elementary synaptic memory form, long-term potentiation.