Glutamate as a Neurotransmitter


Glutamate is a major excitatory neurotransmitter in the vertebrate central nervous system (CNS). Glutamate is released from vesicles that reside at axon terminals of neurons that use this amino acid as a neurotransmitter. Vesicular release is triggered by the arrival of a brief electrical signal (the action potential) at the presynaptic terminal. Most neurons in the vertebrate CNS, even if they themselves do not use glutamate as a neurotransmitter, are contacted by glutamate presynaptic terminals. Glutamate receptors mediate signalling initiated by glutamate release and are involved in plastic changes in the nervous system. These receptors fall into two classes: G protein coupled (metabotropic) and ligand‐gated ion channels (ionotropic). Ionotropic glutamate receptor activation on the target cell initiates a brief electrical depolarisation, which if large enough, causes an action potential in the target cell, and the cycle of signalling begins again. Excessive activation of glutamate receptors can cause neurotoxicity.

Key Concepts:

  • Glutamate is used as a neurotransmitter at the majority of synapses in the vertebrate CNS.

  • Glutamate generally has an excitatory action on target neurons, increasing the probability of action potential 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.

Schematic representation of a glutamate spiny synapse.

Figure 2.

Schematic representations of an ionotropic glutamate receptor subunit (a), metabotropic receptor (b) and a plasma‐membrane glutamate transporter (c). (a) The cartoon depicts the membrane topology of AMPA, NMDA and kainate receptor subunits. A functional receptor comprises four of these subunits. M1, M3, and M4 are regions of the protein that traverse the plasma membrane. The darkened regions of the subunit denote extracellular regions of the protein that contribute to glutamate (Glu) binding. The reentrant loop (M2) contributes to the pore region of the receptor channel and allows cations to pass through upon glutamate binding. (b) A schematic depiction of a metabotropic glutamate receptor. The shaded part of the large N‐terminus represents the glutamate binding pocket of the receptor. Note the seven‐transmembrane domains (M1–M7). Unlike the ionotropic receptors, no pore region is present. (c) Schematic depiction of a plasma‐membrane glutamate transporter. The binding pocket for glutamate is thought to be associated with a reentrant loop structure (M8) reminiscent of the pore region of ionotropic receptors.



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Further Reading

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How to Cite close
Mennerick, Steven, and Zorumski, Charles F(Sep 2012) Glutamate as a Neurotransmitter. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000139.pub3]