Experimental down-regulation of the NMDA channel associated with synapse pruning

Abstract

The N-methyl-D-aspartate (NMDA) receptor has been implicated in activity-dependent synapse stabilization, but its role as a detector of correlated activity during development is debated. In the amphibian retinotectal system, synaptic sorting and stabilization occur throughout larval life, and map refinement is dependent on continuous NMDA receptor function. Moreover, tadpole recta chronically treated with NMDA selectively fail to maintain retinal synapses wherever their activity correlations are lowest. To determine whether this synapse elimination is associated with a specific down-regulation of NMDA receptor function, whole cell voltage-clamp recordings were made from single neurons in tectal slices. After chronic NMDA treatment, decreases in the magnitude of NMDA currents were detected in glutamatergic synaptic currents, in agonist-evoked currants, and in single- channel currents activated by NMDA. The results suggest that the efficacy of NMDA receptors on rectal neurons determines the amount of correlation required to stabilize sets of rectal inputs during formation of the retinotectal projection.