Molecular and anatomical evidence for the input pathway- and target cell type-dependent regulation of glutamatergic synapses.

Glutamate mediates most fast excitatory transmission in the central nervous system by activating primarily two types of ionotropic glutamate receptors: α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors. Differential subunit combinations generate great functional diversity in both categories of receptors, making them highly suitable for meeting complex functional requirements. Converging evidence has indicated that distinct AMPA and NMDA receptor subtypes are selectively targeted to functionally different synapses according to different factors, including presynaptic inputs, postsynaptic cell types, and synaptic configurations. This article provides an overview of recent progress in understanding the basic principles governing the synaptic allocation of AMPA and NMDA receptors, and discusses the underlying mechanisms and functional implications.