Developmental changes in ionotropic glutamate receptors: Lessons from hippocampal synapses

Glutamatergic synapses are the primary source of excitatory transmission in the central nervous system (CNS), and their formation is critical in the establishment of neuronal connections. The refinement of these connections occurs during development and also it is postulated during learning and memory. Recent progress in understanding the molecular components of synaptic junctions, together with advances in imaging techniques, has started to offer new insights into the development of excitatory synapses. Studies performed on low-density primary neuronal cultures have enabled dissection of the temporal sequence of events, which have lead to the differentiation of pre- and postsynaptic components. A central feature of the development of excitatory synapses is the accumulation of glutamatergic receptors (GluRs) at the postsynaptic site. These receptors need to be localized and fixed opposite nerve terminals that release glutamate. But for this to occur, neurons require intracellular anchoring molecules, as well as mechanisms that ensure the efficient turnover and transport of receptor proteins. This review focuses on some of the developmental changes observed in the subcellular distribution and molecular organization of AMPA and NMDA type ionotropic GluRs (iGluRs), which mediate the majority of fast excitatory neurotransmission in the CNS.