NOS inhibition during postnatal development leads to increased ipsilateralretinocollicular and retinogeniculate projections in rats

Synthesis of nitric oxide (NO) occurs downstream from activation of N-methy l-d-aspartate (NMDA) receptors; NO reportedly acts as a retrograde messenge r, influencing the refinement and stabilization of coactive afferent termin als. Cells and neuropil in the rat superior colliculus (SC) and lateral gen iculate body (LGB) show intense, developmentally regulated activity for NO synthase (NOS). To study the role of NO in the development of retinogenicul ate and retinotectal axon arbors, we examined primary visual projections of rats that had received intraperitoneal injections of N-omega-nitro-l-argin ine (L-NoArg, an NOS inhibitor) on postnatal day 0, and daily thereafter fo r 4-6 weeks. Treated rats showed significant alterations in ipsilateral ret inotectal projections, in the mediolateral and anteroposterior axes; there was an increase in the density of fibres entering the SC, in branch length, and in the numbers of boutons on retinotectal arbors in the treated group. Ipsilaterally projecting retinal axons also showed an increase in density and distribution in the dorsal nucleus of the LGB. If animals were allowed to survive for several months after stopping treatment, similar changes wer e also noted, but these were much less striking. Our results support the hy pothesis that, in the mammalian visual system, NO released from target neur ons in the SC and LGB serves as a retrograde signal which feeds back on ret inal afferents, influencing their growth. The effects of NOS inhibition are partially reversed after treatment is stopped, indicating that lack of NO synthesis delays the maturation of retinofugal connections, and also that N O plays a constitutive role in their development.