RETINAL ACTIVITY REGULATES DEVELOPMENTAL SWITCHES IN FUNCTIONAL-PROPERTIES AND IFENPRODIL SENSITIVITY OF NMDA RECEPTORS IN THE LATERAL GENICULATE NUCLEUS

Previous studies have shown that marked changes occur in the kinetic p roperties of N-methyl-D-aspartate (NMDA) receptors during development of the visual pathways. In the lateral geniculate nucleus (LGN) of the ferret, excitatory postsynaptic currents (EPSCs) induced by activatio n of NR?DA receptors display a very slow decay time during the first p ostnatal month, then become shorter in duration following eye-opening (around postnatal day 32; P32). In view of the critical role that NMDA receptors play in activity-dependent refinement of visual connections during development, we have examined the mechanisms that underlie the se changes and how they are regulated. To examine the role of retinal activity, whole-cell recordings were conducted in the LGN slice prepar ation obtained from normal ferrets and ferrets treated with continuous intraocular application of tetrodotoxin (TTX) from P25 until the time of recording. Blockade of ganglion cell activity with TTX prevented t he changes in decay rate of the postsynaptic current induced by NMDA r eceptors. Treated animals older than P40 had NMDA-EPSCs markedly longe r in duration than normal animals at a similar age, resembling respons es present in normal newborn animals, To examine whether changes in su bunit composition of the NMDA receptor may contribute to the maturatio n of its kinetic properties, we used the antagonist ifenprodil, which produces selective inhibition of heteromeric NMDA receptors containing the NR-2B subunit. Ifenprodil induced profound inhibition of NMDA rec eptor activity in normal young animals and TTX-treated mature animals, but substantially less inhibition in normal mature animals, These fin dings indicate that retinal activity is required for the developmental switch from a juvenile form of the NMDA receptor to a more mature for m, possibly affecting NR2 subunit expression. (C) 1997 Elsevier Scienc e B.V.