Experience-Dependent Plasticity and the Maturation of Glutamatergic Synapses

Early Development of Glutamatergic Synaptic Currents The majority of fast excitatory neurotransmission in the CNS is mediated by ionotropic glutamate receptors, which are divided into NMDA, AMPA, and kainate receptor subtypes on the basis of the biophysical properties of their currents, their sensitivity to different pharmaco-Glutamatergic synaptic currents undergo a characteris-logical agents, and the classification of their subunits into distinct genetic families. Both AMPA and NMDA tic pattern of maturation during early development. This receptors are usually colocalized at individual synapses, pattern involves changes in the kinetics of N-methyl-D-so that the synaptic release of glutamate typically acti-aspartate (NMDA) receptor currents and, possibly, the vates both AMPA and NMDA receptor currents on the formation of " silent " synapses that express only NMDA postsynaptic neuron (Nicoll et al., 1990). However, the receptor currents and are later made functional by the ratio of AMPA to NMDA currents at a given synapse addition of ␣-amino-3-hydroxy-5-methyl-4-isoxazole-depends on the identity and maturational stage of the proprionate (AMPA) receptor currents. These matura-synapse (e. During early development, tions for the early development of neural networks (Cline several distinct changes in the properties of gluta-et al., 1996) and for the mechanisms underlying long-matergic synaptic currents have been proposed to oc-term potentiation (LTP) of synaptic efficacy (Malenka cur that alter this ratio of AMPA to NMDA receptor cur-and Nicoll, 1997). Here, we suggest that this pattern of rents. Here, we discuss the functional implications of synaptic maturation also has important implications for two of these changes. understanding how already functional networks are Changes in the Kinetics of NMDA Receptor Currents adaptively modified by the experience of the individual The first developmental change, which is supported by animal during later stages of development and possibly a large body of evidence, is that the amount of current into adulthood. passed by NMDA receptors is initially much greater than Early in development, functional circuits are estab-in adults and then declines rapidly with age and synaptic lished by axonal pathfinding, target selection, synapto-activity. This phenomenon was first observed in layers genesis, and activity-dependent refinement of synaptic IV–VI of the kitten's primary visual cortex in vivo, where connections. Later in development, these initial circuits visual responses are initially highly sensitive to block-may undergo extensive adaptive modification by sen-ade by the NMDA receptor antagonist 2-amino-5-phos-sory and motor experience. This late developmental pe-phonovaleric acid (AP5), and this sensitivity declines riod occurs while the animal is a …