ENHANCED ACTIVATION OF NMDA RECEPTOR RESPONSES AT THE IMMATURE RETINOGENICULATE SYNAPSE

The maturation of retinogeniculate excitatory transmission and intrath alamic inhibition was studied in slices of the dorsal LGN obtained fro m ferrets during the first 2 postnatal months. Response to optic tract stimulation at neonatal ages consisted of slow EPSPs lasting several hundred milliseconds. Application of the NMDA receptor antagonist D-(- )-2-amino-5-phosphonovaleric acid (D-APV) during the first 2 postnatal weeks resulted in EPSPs that were reduced in peak amplitude and drama tically curtailed in duration, indicating that NMDA receptors particip ate strongly in retinogeniculate transmission at the immature synapse. Gradually, EPSPs became shorter in duration such that after the secon d postnatal week, the retinogeniculate EPSPs were only a few milliseco nds in duration. At this late stage of development responses were rema rkably less affected by application of D-APV. These changes in contrib ution of NMDA receptors to retinogeniculate transmission were found to be due to the development of strong IPSPs, the result of gradual matu ration of activation of GABAergic inhibition. Indeed, application of b icuculline methiodide to block GABA, receptor-mediated IPSPs strongly enhanced the NMDA component of the EPSPs in more mature cells. The vol tage dependence and kinetics of NMDA-induced excitatory postsynaptic c urrents (NMDA EPSCs) were characterized by voltage-clamp recordings af ter blocking AMPA/ kainate receptors with 6-cyano-7-nitroquinoxaline-2 ,3-dione and GABA, receptors with bicuculline methiodide. The voltage dependence of the NMDA EPSCs remained unaltered with age. During the f irst postnatal month the kinetic properties of the NMDA EPSCs also rem ained unaltered, but a reduction in EPSC duration was observed within the following weeks, well after the critical period of anatomical reor ganization. The present results demonstrate that the contribution of N MDA ionophores to retinogeniculate transmission is enhanced during the developmental critical period of remodeling in retinogeniculate conne ctivity. This transient enhancement appears to result largely from the late development of GABAergic inhibition, although changes in intrins ic membrane properties and properties of the NMDA ionophore may also c ontribute. Enhanced contribution of NMDA receptors may facilitate anat omical rearrangements or retinogeniculate connections during developme nt.