MODULATION OF NMDA RECEPTOR FUNCTION - IMPLICATIONS FOR, VERTEBRATE NEURAL DEVELOPMENT

The NMDA subtype of glutamate receptor is hypothesized to mediate syna ptic competition in the developing brain by stabilizing converging syn apses that have correlated activity patterns. Disruption of NMDA recep tor function during development interferes with synapse elimination an d sensory map formation. Moreover, many studies indicate that NMDA rec eptor function is high during times of synaptic rearrangement. In this review, a corollary of the NMDA receptor hypothesis for activity-depe ndent synapse stabilization is proposed. As developing inputs increase in number and strength, the increasing excitatory synaptic activity i n young neurons should lead to increases in postsynaptic Ca2+ influx t hrough NMDA receptors. This Ca2+ flux is postulated to trigger a feedb ack system that changes the subunit composition of the NMDA receptor c omplex so that less Ca2+ enters postsynaptic cells upon NMDA receptor activation. Changes in NMDA receptor effectiveness resulting from mani pulations of activity are consistent with the idea that NMDA receptor function is under the control of activity. This postulate of activity- dependent control of NMDA receptor expression has implications for the control of brain plasticity. If particular combinations of NMDA recep tor subunits typically expressed in young animals are better than adul t receptor types at maintaining synapses in regions where they are not well correlated with other inputs, then expression of these juvenile subunit combinations could facilitate synaptic rearrangements in the m ature brain after the normal end of synaptic plasticity. Thus, underst anding the regulation of NMDA receptor function during development cou ld provide a novel approach to restructuring circuitry in the adult br ain to compensate for damage produced by trauma or disease.