Cholinergic Potentiation of Restoration of Visual Function after Optic Nerve Damage in Rats

Abstract

Enhancing cortical plasticity and brain connectivity may improve residual vision following a visual impairment. Since acetylcholine plays an important role in attention and neuronal plasticity, we explored whether potentiation of the cholinergic transmission has an effect on the visual function restoration. To this end, we evaluated for 4 weeks the effect of the acetylcholinesterase inhibitor donepezil on brightness discrimination, visually evoked potentials, and visual cortex reactivity after a bilateral and partial optic nerve crush in adult rats. Donepezil administration enhanced brightness discrimination capacity after optic nerve crush compared to nontreated animals. The visually evoked activation of the primary visual cortex was not restored, as measured by evoked potentials, but the cortical neuronal activity measured by thallium autometallography was not significantly affected four weeks after the optic nerve crush. Altogether, the results suggest a role of the cholinergic system in postlesion cortical plasticity. This finding agrees with the view that restoration of visual function may involve mechanisms beyond the area of primary damage and opens a new perspective for improving visual rehabilitation in humans.

Cholinergic Potentiation Alters Perceptual Eye Dominance Plasticity Induced by a Few Hours of Monocular Patching in Adults

“…Specifically, repeated days of cholinergic enhancement has been shown to improve visual perceptual learning for a number of tasks in observers with normal vision (Rokem and Silver, 2010; Kang et al, 2014; Chamoun et al, 2017a), suggesting a central role of the neurotransmitter in modulating plasticity processes. In the rat, cholinergic potentiation also improves visual recovery (Chamoun et al, 2017b) and visual processing (Soma et al, 2013; Kang et al, 2015; Chamoun et al, 2016), due, in part, to enhancing the responsiveness of visual neurons to their tuned stimuli. Based on these findings, we expected a reinforcement of the shift in perceptual eye dominance in favor of the deprived eye.…”

Protective Efficacy of a Dietary Supplement Based on Forskolin, Homotaurine, Spearmint Extract, and Group B Vitamins in a Mouse Model of Optic Nerve Injury

“…Following surgery, mice did not exhibit any abnormal eating and drinking behavior. The optic nerves of both eyes were crushed in agreement with previous studies [25,26] and the effects of ONC in operated and in control mice were then compared. In this respect, there are some limitations to the use of the non-damaged eye as an internal control for a number of reasons.…”

Mesoscopic cortical network reorganization during recovery of partial optic nerve injury in GCaMP6s mice

“…Similarly, our mice did not appear to detect the cliff as indicated by the loss of avoidance behaviors during the visual cliff test. Previous rat studies showed a disconnection between behavior and anatomical or electrophysiological changes following damage to the optic nerve 9 . In these studies, it was shown that even with only 10% of functional retinal ganglion cells, the animals were able to perform close to normal in behavioral visual tasks 26 .…”

“…This recovery is in agreement with previous autoradiographic studies after an ONC in rats 26 . Other studies were unable to observe an improvement in cortical activity following an ONC using visual evoked potential (VEP) recordings 9,27,28 in anesthetized rats. The calcium signal of GCAMP6s mice mainly arises from the Thy-1 long-projecting excitatory neurons and is not detected in GABAergic cells 29 .…”

“…The partial optic nerve crush (ONC) in adult rodents can be used as a model to simulate the visual deficits of diseases such as traumatic optic neuropathy, glaucoma, optic neuritis or immunemediated CNS demyelination 7 , and its intensity determines the degree of vision loss. Spontaneous visual recovery occurs in this model with up to 20% gain of function, as shown in a contrast discrimination task or visually guided behavior in rats and mice 5,[8][9][10] . The extent of residual vision depends on the number of surviving retinal cells and their axons, as well as cortical plasticity mechanisms, including functional connectivity reorganization 5,11 .…”