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

A Vercelli, D Garbossa, S Biasiol, M Repici, S Jhaveri

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Synthesis of nitric oxide (NO) occurs downstream from activation of N-methyl-D-aspartate (NMDA) receptors; NO reportedly 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 intraperitoneal injections of Nomega-nitro-L-arginine (L-NoArg, an NOS inhibitor) on postnatal day 0, and daily thereafter for 4-6 weeks. Treated rats showed significant alterations in ipsilateral retinotectal 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 were also noted, but these were much less striking. Our results support the hypothesis 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. 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 NO plays a constitutive role in their development.

Original languageEnglish
Pages (from-to)473-490
Number of pages18
JournalEuropean Journal of Neuroscience
Issue number2
Publication statusPublished - Feb 2000


  • Animals
  • Animals, Newborn
  • Axons/ultrastructure
  • Blood Pressure/drug effects
  • Calcium Channel Blockers/pharmacology
  • Enzyme Inhibitors/pharmacology
  • Geniculate Bodies/enzymology
  • Glutamic Acid/physiology
  • Isoenzymes/antagonists & inhibitors
  • Nerve Tissue Proteins/antagonists & inhibitors
  • Nitric Oxide/physiology
  • Nitric Oxide Synthase/antagonists & inhibitors
  • Nitroarginine/pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate/physiology
  • Retina/growth & development
  • Superior Colliculi/enzymology
  • Vasodilation
  • Verapamil/pharmacology
  • Visual Pathways/growth & development


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