Recovery from the anatomical effects of long‐term monocular deprivation in cat lateral geniculate nucleus

Abstract

Monocular deprivation (MD) imposed early in postnatal life elicits profound structural and functional abnormalities throughout the primary visual pathway. The ability of MD to modify neurons within the visual system is restricted to a so-called critical period that, for cats, peaks at about one postnatal month and declines thereafter so that by about 3 months of age MD has little effect. Recovery from the consequences of MD likewise adheres to a critical period that ends by about 3 months of age, after which the effects of deprivation are thought to be permanent and without capacity for reversal. The attenuation of plasticity beyond early development is a formidable obstacle for conventional therapies to stimulate recovery from protracted visual deprivation. In the current study we examined the efficacy of dark exposure and retinal inactivation with tetrodotoxin to promote anatomical recovery in the dorsal lateral geniculate nuclues (dLGN) from long-term MD started at the peak of the critical period. Whereas 10 days of dark exposure or binocular retinal inactivation were not better at promoting recovery than conventional treatment with reverse occlusion, inactivation of only the non-deprived (fellow) eye for 10 days produced a complete restoration of neuron soma size, and also reversed the significant loss of neurofilament protein within originally deprived dLGN layers. These results reveal a capacity for neural plasticity and recovery that is larger than anything previously observed following protracted MD in cat, and they highlight a possibility for alternative therapies applied at ages thought to be recalcitrant to recovery.

Retinal and Optic Nerve Integrity Following Monocular Inactivation for the Treatment of Amblyopia

“…These limitations notwithstanding, results of these studies demonstrate the potential for recovery at ages not responsive to typical treatments. In a recent study using cats, temporary inactivation of retinal ganglion cells in the fellow eye using tetrodotoxin (TTX), FIGURE 1 | Summary of data from Duffy et al (2018) that examined the recovery of neuron soma size (open circles) and neurofilament labeling (closed circles) in the lateral geniculate nucleus of monocularly deprived cats. Six weeks of monocular deprivation (MD) started at the peak of the critical period for plasticity produced a large deprivation effect with deprived neurons rendered about ∼35% smaller than neurons connected to the non-deprived eye, and deprived layers showing a ∼55% reduction in the density of neurofilament-positive neurons.…”

Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex

“…In rats, spatial acuity in the deprived eye is undetectable 25 following cMD initiated at eye opening (Eaton et al, 2016). Additionally, following 26 prolonged monocular deprivation, neurons in the dorsal lateral geniculate nucleus 27 (dLGN) that project to deprived binocular visual cortex have lower metabolism (Kennedy 28 et al, 1981) and smaller somata (Duffy et al, 2018). Chronic monocular deprivation 29 (cMD) also significantly decreases the density of dendritic spines on pyramidal neurons 30 in deprived V1b (Montey and Quinlan, 2011) and results in a 60% decrease in the 31 thalamic component of the visually evoked potential (VEP, ( Montey and Quinlan, 32 2011)).…”

Therapeutic effect of vasoactive intestinal peptide on form-deprived amblyopic kittens

“…Based on the experimental results, VIP undeniably has a therapeutic effect on the visual nervous system. Some studies have found that LGBd function in form-deprived amblyopic kittens can be partially restored after the sensitive period of visual development [40], which is worthy of our next study. LGBd, increased the expression of VIP, shortened the latency of the P100 wave and increased its amplitude in amblyopic eyes.…”