Glutamate as a Neurotransmitter


Glutamate is an amino acid used in biochemical pathways of all cells, but it is also packaged and released as a neurotransmitter from many neurons in the vertebrate central nervous system (CNS). Glutamate is released at specific junctions, synapses, between a glutamate‐releasing neuron and target neurons that express surface receptors for glutamate. Most neurons in the vertebrate CNS, even if they themselves do not use glutamate as a neurotransmitter, have glutamate receptors. Glutamate receptors initiate electrical and biochemical signals in the target cell and can induce changes in strength of signalling that neuroscientists believe underlie the ability of thoughts and behaviours to change with experience. Glutamate receptors fall into two classes: ligand‐gated ion channels (ionotropic) and G protein coupled (metabotropic). In addition to propagating and modulating normal electrical signalling, glutamate receptors, activated excessively, can cause neurotoxicity in disease states.

Key Concepts

  • Glutamate is used as a neurotransmitter at the majority of synapses in the vertebrate CNS.
  • Glutamate typically has an excitatory action on target neurons, increasing the probability of electrical impulse firing in the target.
  • Glutamate acts through G protein‐coupled receptors and through ligand‐gated ion channels.
  • Glutamate synapses exhibit remarkable plasticity (malleability) that may play an important role in memory formation.
  • In excess glutamate can be neurotoxic, acting through the same glutamate receptors that mediate normal signalling.

Keywords: excitatory; spine; excitotoxicity; NMDA; long‐term potentiation

Figure 1. The site of glutamate synapses is typically on dendritic spines. (a) A typical neuron with dendrites (receiving part of the neuron) near the cell body, a long axon (the sending branch of the neuron), and axon terminals, where transmitter is released. The red box indicates a dendrite segment which, in some neuronal types, will contain dendritic spines (magnified in panel b) are located. Spines exhibit varied shapes but are typical recipients of glutamate synapses (panel c). The presynaptic axon terminal in panel c contains vesicles filled with glutamate. The postsynaptic spine contains recipient receptors. Astrocytes nearby are responsible for the bulk of glutamate removal following synaptic release and receptor activation.
Figure 2. Glutamate receptors. (a) Cartoon structures of ionotropic (iGluRs) and metabotropic (G protein‐coupled; mGluRs) receptors. Different receptor domains are indicated: Amino terminal domain (ATD), ligand‐binding domain (LBD), transmembrane domain (TMD), C‐terminal domain (CTD), and cysteine‐rich domain (CTD). Also shown are allosteric modulators (ligands that bind at sites distinct from the transmitter), which can influence receptor activation positively or negatively for therapeutic or experimental purposes. Channel blockers are drugs that occlude ion flow through the channel of ionotropic channels. (b) Responsiveness of various receptors to varied concentrations of glutamate, and the typical physiological concentrations of glutamate achieved in various cellular and extracellular compartments. Reiner, A., & Levitz, J. . Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert. Neuron, 98(6), 1080–1098. doi:10.1016/j.neuron.2018.05.018. © 2018 Elsevier.


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Lambert, Peter, and Mennerick, Steven(Aug 2020) Glutamate as a Neurotransmitter. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0029140]