Glutamatergic Synapses: Molecular Organisation

Abstract

One of the best understood and highly organised synapses is excitatory glutamatergic synapses. These synapses consist of post‐synaptic ionotropic glutamate receptors and pre‐synaptic glutamate localised inside pre‐synaptic vesicles. Glutamate binds to α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid subtype glutamate receptors, giving rise to synaptic transmission. However, N‐methyl‐d‐aspartate subtype glutamate receptors function to induce the change in synaptic transmission, also known as the synaptic plasticity that underlies learning and memory. The subtypes and subunits of glutamate receptors exhibit distinct biophysical properties and play distinct physiological roles critical for synaptic function. The molecular organisation of the synapse includes intracellular scaffolding proteins, intercellular cell adhesion molecules to anchor synaptic architecture and a variety of signalling proteins (kinases, phosphatases, etc.). They function to support and/or mediate the cellular processes critical for synaptic transmission and plasticity, whereas their malfunction leads to diseases where synaptic plasticity is lost, such as Alzheimer disease and mental retardation.

Key Concepts:

  • Glutamatergic synapses are critical for our brain function.

  • Synaptic plasticity is critical for proper neuronal circuit formation.

  • Synaptic plasticity is the cellular model for learning, memory and other experience‐dependent brain functions.

  • History of neuronal activity plays a significant role in synaptic protein composition, which in turn governs synapse‐to‐nucleus signalling.

  • Scaffolding proteins, in addition to signalling proteins and receptors, are critical for synaptic plasticity.

  • Extrasynaptic NMDA receptor signalling plays distinct roles from synaptic NMDA receptor signalling.

Keywords: glutamate; synapse; AMPA receptors; synaptic plasticity; LTD; LTP; post‐synaptic density (PSD); scaffolding proteins; synaptic scaling; extrasynaptic NMDA receptors

Figure 1.

Synaptic transmission at basal state: glutamate ( ) released from synaptic terminal diffuses across synaptic cleft, binds to, and opens AMPA subtype glutamate receptors (AMPAR), leading to membrane depolarisation. NMDA subtype glutamate receptors (NMDAR) do not open because of magnesium ion ( ) blockade of channel pore. Extrasynaptic AMPAR and NMDAR do not have access to released glutamate because of clearance by glutamate transporters (Glu T) localised in glia or pre‐synaptic terminal.

Figure 2.

Schematics of scaffolding proteins, cell adhesion molecules (CAM) and signalling proteins in synapse organisations and plasticity. (a) PDZ domain containing scaffolding proteins: PSD95 and GRIP as two examples. (b) Signalling enzymes and their targeting proteins: CaMKII/PKA and PP1/PP2B along with their targeting proteins (NMDAR, AKAP79/150 and neurabin). (c) CAMs: NLG: neuroligin family CAMs, has four isoforms; LRRTM has at least four isoforms; N‐cadherin has many isoforms.

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Chen L, Tracy T and Nam CI (2007) Dynamics of postsynaptic glutamate receptor targeting. Current Opinion in Neurobiology 17(1): 53–58.

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Siddoway, Benjamin, Hou, Hailong, and Xia, Houhui(Dec 2011) Glutamatergic Synapses: Molecular Organisation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000235.pub2]