The glutamatergic nerve terminal

Abstract

Glutamate as a neurotransmitterThe human brain has about lolo neurones, each of which, on average, makes about 1000 synaptic contacts with other neurones. Of these l O I 3 synapses perhaps up to 90% utilize amino acids as their neurotransmitter. Glutamate is the major excitatory amino acid (acting predominantly on depolarizing post-synaptic receptors) while 4-aminobutyrate (GABA) and glycine are the major inhibitory transmitters (acting on hyper-polarizing receptors). As well as playing the dominant role in fast information transfer, glutamate is of particular interest in view of its involvement in current models of memory and learning (Bliss and Dolphin, 1982;Cotman et al., 1988;Collingridge and Singer, 1990) and because a pathological release of glutamate in brain ischaemia is neurotoxic and a major contributor to the damage caused under these conditions (Rothman and Olney, 1986;Choi, 1988 ;Meldrum and Garthwaite, 1990).A synapse has a pre-synaptic element responsible for the storage and release of transmitter and a post-synaptic element containing one or more classes of receptor for the transmitter. The potent combination of electrophysiology and molecular cloning has allowed a dramatic advance in our understanding of post-synaptic events. Three classes of post-synaptic ionotropic (possessing an integral ion channel) glutamate receptors have been identified and cloned: the 2-amino-3-hydroxy-5-methyl-4-isoxazole propionatekainate (AMPA/ KA) receptor Nakanishi et al., 1990;Sakmann, 1992), the high-affinity KA receptor (Egebjerg et al., 1991) and the N-methyl D-aSpartate (NMDA) receptor (Moriyoshi et al., 1991 ; Kumar et al., 1991 ;Barnard, 1992). Each can exist in many isoforms by combining subunits formed from distinct genes, by alternative splicing or by post-transcriptional modification (Monyer et al., 1991 ;Burnashev et al., 1992).The AMPNKA receptor is responsible for fast information transfer while the NMDA receptor is only operative when the post-synaptic membrane is independently depolarized by another receptor. This 'associative' behaviour of the latter is believed to underlie aspects of the learning process.

Quantification of the synaptosomal proteome of the rat cerebellum during post-natal development

“…Membrane potential is generated by a precise distribution of ions (Na ) across the membrane. Enzymes utilizing ATP, ATPases, are required to move ions against their gradients across the membrane to maintain and regulate membrane potential at the synapses, which is essential for neurotransmitter release (McMahon and Nicholls 1991;Nicholls 1993). We observed a variety of ATPases that increased during the experimental time course (Fig.…”

Activation of phospholipase D by metabotropic glutamate receptor agonists in rat cerebrocortical synaptosomes

“…Synaptosomes remain functionally intact only for periods of up to 6 h (Nicholls, 1993). This life-span may not be su cient to achieve equilibrium of labelling with [ 3 H]-inositol.…”

Enrichment of presynaptic and postsynaptic markers by size‐based gating analysis of synaptosome preparations from rat and human cortex

“…The synaptosome preparation has enabled detailed study of the brain's functional unit, the synapse, which is technically difficult to isolate and examine. Synaptosomes are considered a primarily presynaptic preparation (2), consistent with the vesicle-filled profiles most commonly observed using EM (3,4). However, the postsynaptic element may remain attached opposite the postsynaptic density as an intact "neurosome" (2,5).…”