Nogo-A deletion increases the plasticity of the optokinetic response and changes retinal projection organization in the adult mouse visual system

Abstract

The inhibitory action of Nogo-A on axonal growth has been well described. However, much less is known about the effects that Nogo-A could exert on the plasticity of neuronal circuits under physiological conditions. We investigated the effects of Nogo-A knock-out (KO) on visual function of adult mice using the optokinetic response (OKR) and the monocular deprivation (MD)-induced OKR plasticity and analyzed the anatomical organization of the eye-specific retinal projections. The spatial frequency sensitivity was higher in intact Nogo-A KO than in wild-type (WT) mice. After MD, Nogo-A KO mice reached a significantly higher spatial frequency and contrast sensitivity. Bilateral ablation of the visual cortex did not affect the OKR sensitivity before MD but reduced the MD-induced enhancement of OKR by approximately 50% in Nogo-A KO and WT mice. These results suggest that cortical and subcortical brain structures contribute to the OKR plasticity. The tracing of retinal projections to the dorsal lateral geniculate nucleus (dLGN) revealed that the segregation of eye-specific terminals was decreased in the adult Nogo-A KO dLGN compared with WT mice. Strikingly, MD of the right eye led to additional desegregation of retinal projections in the left dLGN of Nogo-A KO but not in WT mice. In particular, MD promoted ectopic varicosity formation in Nogo-A KO dLGN axons. The present data show that Nogo-A restricts visual experience-driven plasticity of the OKR and plays a role in the segregation and maintenance of retinal projections to the brain.

Restoring GM1 ganglioside expression ameliorates axonal outgrowth inhibition and cognitive impairments induced by blast traumatic brain injury

“…Another inhibitory myelin protein, NOGO was reported in many studies to play a cardinal role in the inhibitory effect of myelin243637. Suppressing its expression in neural cultures as well as in animal models prevented the axonal outgrowth inhibition38394041. Preliminary results of NOGO expression by immunofluorescence staining showed an elevation in the cortices of the injured brains and that GM1 administration prevented this elevation (data not shown).…”

Nogo‐A inhibits vascular regeneration in ischemic retinopathy

“…We have previously reported that glia-specific inactivation of Nogo-A increased retinal ganglion cell plasticity after optic nerve injury (Vajda et al, 2015) and after monocular deprivation in intact animals (Guzik-Kornacka et al, 2016). In the brain, the Nogo-A-S1PR2 ligandreceptor pair may also operate in the mechanisms controlling blood vessel plasticity after stroke.…”

Nogo-A-targeting antibody promotes visual recovery and inhibits neuroinflammation after retinal injury

“…To evaluate the visual acuity of freely moving mice, the optokinetic reflex was tested using OptoDrum system (Striatech GmbH Vor dem Kreuzberg, Tübingen, Germany). In brief, mice (6-9/group) were placed on a platform in the middle of an arena surrounded by four computer screens while moving gratings of different spatial frequencies were passed on the monitors 36,37 . The reflexive tracking movement of the mouse neck in the temporal-to-nasal direction allowed to evaluate the visual response of the two eyes separately by changing the direction of the visual stimulus.…”

“…This mechanism deserves to be tested in the injured visual system. It may allow to explain why the plasticity of RGC terminals is increased in the dorso lateral geniculate nucleus of Nogo-A KO mice after monocular deprivation, for example 36 . A similar mechanism may operate after retinal excitotoxicity.…”