Chronic NMDA Receptor Blockade From Birth Delays the Maturation of NMDA Currents, but Does Not Affect AMPA/Kainate Currents

Abstract

The activity of the N-methyl-d-aspartate receptor (NR) regulates the composition of excitatory synapses and mediates multiple forms of synaptic and structural plasticity. In the superficial superior colliculus (sSC) of the rat, NR activity is essential for the full refinement of retinotopy during development. We have examined the NR's role in synaptic development by chronically treating the sSC from birth with the competitive antagonist (±)-2-amino-5-phosphonopentanoic acid (AP5) released by the slow-release polymer Elvax. Whole-cell voltage-clamp recordings were used to characterize excitatory postsynaptic potentials (EPSCs) in slices from postnatal day (P)12–20 sSC. Chronic NR blockade reduced the ratio of AMPA/kainate receptor (AMPAR) to NR peak current amplitudes of both spontaneous (s)EPSCs and evoked EPSCs. Spontaneous NR current amplitude was increased following treatment, while spontaneous AMPAR currents were identical to those of controls, indicating that the ratio change was due to an increased NR current. Comparison of sEPSC frequency, AMPAR current rectification, and quantitative Western blots indicated that the characteristics of AMPARs at the synapse are normal following AP5 treatment. In the sSC, NR currents show a rapid decrease in decay time on P11 and previous studies in slices indicate this change results from a NR-mediated activation of the phosphatase calcineurin. Consistent with this in vitro finding, the down-regulation failed to occur in sSC chronically treated with AP5 in vivo. Together the present data show that NR function is necessary for subsequent NR current regulation in vivo, but it is not essential for the developmental expression of normal AMPAR currents.