Developmental period for N-methyl-D-aspartate (NMDA) receptor-dependent synapse elimination correlated with visuotopic map refinement.
During a short perinatal interval, N-methyl-D-aspartate receptor (NMDAR) function is essential to a process in which spontaneous retinal waves focus retinal axon arbors in the superficial layers of the rodent superior colliculus (sSC). Here we provide evidence that this NMDAR-dependent axonal refinement occurs through elimination of uncorrelated retinal synapses arising from disparate loci, rather than stabilization of topographically appropriate inputs. The density of synaptic release sites within fluorescently labeled retinal terminals was counted in double-labeling experiments using confocal microscopy and antibodies against synaptophysin or synapsin-1. Chronic NMDAR blockade from birth increased retinal axon synapse density at postnatal days (P) 6, 8, and 10, suggesting that NMDAR currents reduce synapse density during the refinement period. With assay at P14, after focal arborization has been established, the effect disappeared. Conversely, chronic NMDA treatment, known to induce functional synaptic depression in the sSC, decreased retinocollicular synapse density at P14, but not earlier, during the refinement period (P8). Thus during the development of retinocollicular topographic order, there is a period when NMDAR activity predominantly eliminates retinal axon synapses. We were able to extend this period by using retinal lesions to reduce synaptic density in a defined zone. Synapse density on intact retinocollicular axons sprouting into this zone was increased by NMDAR blockade, even when examined at P14. Thus, the period of NMDAR-dependent synaptic destabilization is terminated by a factor related to the density and refinement of retinal arbors.
Colonnese
Matthew T
MT
McGovern Institute for Brain Research, Department of Biology, Cambridge, Massachusetts 02139-4307, USA. mcolonne@mit.edu
Constantine-Paton
Martha
M
D000818:Animals; D001369:Axons / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D018709:Statistics, Nonparametric; D013477:Superior Colliculi / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D014795:Visual Pathways / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; D016708:Synaptophysin