Input- and Output-Specific Segregation of Amino Acid Neurotransmitter Receptors on the Surface of Central Neurones

Most nerve cells in the central nervous system receive glutamate, the major excitatory neurotransmitter in the brain, from several distinct sources. For example, pyramidal cells in the CA l area of the hippocampus receive a glutamatergic input from the entorhinal cortex in the stratum lacunosum-moleculare. These cells are also innervated by axon terminals of CA3 pyramidal cells, which also use glutamate as neurotransmitter, mainly in the strata oriens and radiatum, whereas local axon collaterals of the CA 1 pyramidal cells are restricted to the stratum oriens and to the alveus (reviewed by Witter 1993). This multiple glutamatergic innervation of neurones is paralleled by the diversity of glutamate receptors (GIuR) expressed by nerve cells. Three distinct classes of ionotropic GluRs [α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type, kainate-type and N-methyl-D-aspartate (NMDA)-type] have been identified and classified according to their agonist selectivity, physiological properties and amino acid sequence homology between subunits constituting subtypes of these GluRs (reviewed by Seeburg 1993; Hollmann and Heinemann 1994). Several subunits have been discovered within each class, suggesting the existence of dozens of different ionotropic GluR subtypes.