RAPID ACQUISITION OF DENDRITIC SPINES BY VISUAL THALAMIC NEURONS AFTER BLOCKADE OF N-METHYL-D-ASPARTATE RECEPTORS

N-Methyl-D-aspartate (NMDA) receptors play an important role in the de velopment of retinal axon arbors in the mammalian lateral geniculate n ucleus (LGN). We investigated whether blockade of NMDA receptors in vi vo or in vitro affects the dendritic development of LGN neurons during the period that retinogeniculate axons segregate into on-center and o ff-center sublaminae. Osmotic minipumps containing either the NMDA rec eptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV) or saline w ere implanted in ferret kits at postnatal day 14. After 1 week, LGN ne urons were intracellularly injected with Lucifer yellow. Infusion of D -APV in vivo led to an increase in the number of branch points and in the density of dendritic spines compared with age-matched normal or sa line-treated animals. To examine the time course of spine formation, c rystals of -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlor ate were placed in the LGN in brain slices from 14- to 18-day-old ferr ets. Labeled LGN cell dendrites were imaged on-line in living slices b y confocal microscopy, with slices maintained either in normal perfusi on medium or with the addition of D-APV or NMDA to the medium. Additio n of D-APV in vitro at doses specific for blocking NMDA receptors led to a >6-fold net increase in spine density compared with control or NM DA-treated slices. Spines appeared within a few hours of NMDA receptor blockade, indicating a rapid local response by LGN cells in the absen ce of NMDA receptor activation. Thus, activity-dependent structural ch anges in postsynaptic cells act together with changes in presynaptic a rbors to shape projection patterns and specific retinogeniculate conne ctions.