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The Journal of Neuroscience, January 1, 1999, 19(1):229-235

NMDA Receptor-Mediated Refinement of a Transient Retinotectal Projection during Development Requires Nitric Oxide

Alan F. Ernst¹, Hope H. Wu¹, Esam E. El-Fakahany², and Steven C. McLoon¹

¹ Department of Cell Biology and Neuroanatomy and ² Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota 55455

A transient ipsilateral retinotectal projection is normally eliminated during 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 projection 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 ipsilateral retinotectal projection. The effect of NMDA receptor blockade on nitric oxide synthase activity in tectal cells was assessed biochemically in chick embryos. Increasing concentrations of MK-801 resulted in a dose-dependent decrease in nitric oxide synthase activity. This result suggests that NMDA receptor activation can regulate nitric oxide synthase activity in the 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-nitro-L-arginine (L-NoArg). At comparable levels of inhibition of nitric oxide synthesis, no significant difference was observed in the degree of rescue mediated by NMDA receptor blockade or nitric oxide synthesis blockade. These results suggest that NMDA receptor-mediated elimination of the ipsilateral retinotectal projection is completely mediated via nitric oxide.

Key words: NMDA receptor; nitric oxide; nitric oxide synthase; retina; tectum; pattern formation; neuronal development; chick

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Copyright © 1999 Society for Neuroscience  0270-6474/99/191229-07$05.00/0

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