Synaptic environment and extrasynaptic glutamate signals: The quest continues. (1st September 2021)

• Record Type: Journal Article
• Authors: Rusakov, Dmitri A.; Stewart, Michael G.
• Is Part Of: Neuropharmacology. Volume 195(2021)
• Publication Date: 2021-09-01
• Subjects: Synaptic connections -- Synaptic cleft -- Dendritic spines -- Micro-physiology -- Perisynaptic astrocyte processes (PAP) -- Glutamate spillover; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108688
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Behaviour of a mammal relies on the brain's excitatory circuits equipped with glutamatergic synapses. In most cases, glutamate escaping from the synaptic cleft is rapidly buffered and taken up by high-affinity transporters expressed by nearby perisynaptic astroglial processes (PAPs). The spatial relationship between glutamatergic synapses and PAPs thus plays a crucial role in understanding glutamate signalling actions, yet its intricate features can only be fully appreciated using methods that operate beyond the diffraction limit of light. Here, we examine principal aspects pertaining to the receptor actions of glutamate, inside and outside the synaptic cleft in the brain, where the organisation of synaptic micro-physiology and micro-environment play a critical part. 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. Evidence is also emerging that neuronal activity- and astroglia-dependent glutamate spillover actions could be important across the spectrum of cognitive functions This article is part of the special issue on 'Glutamate Receptors - The Glutamatergic Synapse'. Highlights: Glutamatergic excitatory transmission is at the core of information processing in the brain. Excitatory synapses underpin wired connectivity of brain networks. Glutamate may escape the synaptic cleft acting in a volume-transmission mode. Glutamate escape is controled by high-affinity astroglial transporters. Neural activity or pathology may alter astroglial synaptic coverage thus regulating glutamate escape.