NMDA receptor-mediated refinement of a transient retinotectal projection during development requires nitric oxide

A transient ipsilateral retinotectal projection is normally eliminated duri ng embryonic development of the chick visual system. Administration of the NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten- 5,10-imine (MK-801) during the developmental period in which this projectio n normally disappears prevented its complete elimination. Previous studies showed that tectal cells express nitric oxide synthase during development, and blocking synthesis of nitric oxide also prevented elimination of the ip silateral retinotectal projection. The effect of NMDA receptor blockade on nitric oxide synthase activity in tectal cells was assessed biochemically i n chick embryos. Increasing concentrations of MK-801 resulted in a dose-dep endent decrease in nitric oxide synthase activity. This result suggests tha t NMDA receptor activation can regulate nitric oxide synthase activity in t he tectum. The degree of rescue of the ipsilateral retinotectal projection was compared in embryos treated either with MK-801 or with an inhibitor of nitric oxide synthesis, N omega-nitro-L-arginine (L-NoArg). At comparable l evels of inhibition of nitric oxide synthesis, no significant difference wa s observed in the degree of rescue mediated by NMDA receptor blockade or ni tric oxide synthesis blockade. These results suggest that NMDA receptor-med iated elimination of the ipsilateral retinotectal projection is completely mediated via nitric oxide.