Role of nitric oxide in the development of retinal projections

Synthesis of nitric oxide (NO) occurs downstream from activation of NMDA receptors and NO acts as a retrograde messenger, influencing the refinement and stabilization of coactive afferent terminals. Cells and neuropil in the rat superior colliculus (SC) and lateral geniculate body (LGB) show intense, developmentally regulated activity for NO synthase (NOS). To study the role of NO in the development of retinogeniculate and retinotectal axon arbors, we examined primary visual projections of rats that had received daily i.p. injections of L-NoArg (an NOS inhibitor) for 4-6 weeks starting from postnatal day 0. Retinal fibers labeled by intraocular injection of the B subunit of cholera toxin were revealed immunohistochemically and the density of fibers in the superficial SC and in the dorsal LGB was measured by computerized image analysis. Single retinocollicular terminal arbors were reconstructed at the computer (Neurolucida). Treated rats showed significant alterations in ipsilateral retinotectal projections, in the mediolateral and anteroposterior axes: there was an increase in the density of fibers entering the SC, in branch length, and in 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 were also noted, but these were much less striking. Our results suggest that, in the mammalian visual system, NO released from target neurons in the SC and LGB serves as a retrograde signal which feeds back on retinal afferents, influencing their growth.