Failure to disrupt development of cholinergic fiber patches in the superior colliculus in nitric oxide synthase deficient mice

Nitric oxide (NO) has been shown to mediate refinement of glutamatergic axo nal pathways during development. In this study, we investigated whether the development of a cholinergic pathway in the intermediate gray layer (IGL) of the mouse superior colliculus (SC) is also mediated by NO. The pathway w as labeled using an antibody directed against choline acetyltransferase (Ch AT) and its distribution examined in normal C57/BL6 mice and in knockout mi ce in which the genes for the neuronal isoform of nitric oxide synthase (NO S) or both the endothelial and neuronal isoforms of NOS had been disrupted. We also examined the development of expression of NOS using nicotinamide a denine dinucleotide phosphate diaphorase (NADPHd) staining. NADPHd labeled cells were found within the IGL by P8 and formed loose clusters of cells by P12-P15. ChAT and NADPHd labeled fibers were first observed at P12 and gra dually established their characteristic two-tiered patchy pattern between P 14 and P21. Comparison of the ChAT labeled fiber distribution in normal, si ngle nNOS and double e,nNOS knockout mice revealed no differences between t hese three groups. We therefore conclude that nitric oxide does not mediate refinement of this cholinergic pathway. (C) 1999 Elsevier Science B.V. All rights reserved.