From Basic Visual Science to Neurodevelopmental Disorders: The Voyage of Environmental Enrichment-Like Stimulation.

Genes and environmental stimuli cooperate in the regulation of brain development and formation of the adult neuronal architecture. Genetic alterations or exposure to perturbing environmental conditions, therefore, can lead to altered neural processes associated with neurodevelopmental disorders and brain disabilities. In this context, environmental enrichment emerged as a promising and noninvasive experimental treatment for favoring recovery of cognitive and sensory functions in different neurodevelopmental disorders. The aim of this review is to depict, mainly through the much explicative examples of amblyopia, Down syndrome, and Rett syndrome, the increasing interest in the potentialities and applications of enriched environment-like protocols in the field of neurodevelopmental disorders and the understanding of the molecular mechanisms underlying the beneficial effects of these protocols, which might lead to development of pharmacological interventions.

An essential role for the latero-medial secondary visual cortex in the acquisition and retention of visual perceptual learning in mice.

Perceptual learning refers to any change in discrimination abilities as a result of practice, a fundamental process that improves the organism's response to the external environment. Visual perceptual learning (vPL) is supposed to rely on functional rearrangements in brain circuity occurring at early stages of sensory processing, with a pivotal role for the primary visual cortex (V1). However, top-down inputs from higher-order visual areas (HVAs) have been suggested to play a key part in vPL, conveying information on attention, expectation and the precise nature of the perceptual task. A direct assessment of the possibility to modulate vPL by manipulating top-down activity in awake subjects is still missing. Here, we used a combination of chemogenetics, behavioral analysis and multichannel electrophysiological assessments to show a critical role in vPL acquisition and retention for neuronal activity in the latero-medial secondary visual cortex (LM), the prime source for top-down feedback projections reentering V1.

Visual Perceptual Learning Induces Long-Lasting Recovery of Visual Acuity, Visual Depth Perception Abilities and Binocular Matching in Adult Amblyopic Rats.

An abnormal visual experience early in life, caused by strabismus, unequal refractive power of the eyes, or eye occlusion, is a major cause of amblyopia (lazy eye), a highly diffused neurodevelopmental disorder severely affecting visual acuity and stereopsis abilities. Current treatments for amblyopia, based on a penalization of the fellow eye, are only effective when applied during the juvenile critical period of primary visual cortex plasticity, resulting mostly ineffective at older ages. Here, we developed a new paradigm of operant visual perceptual learning performed under conditions of conventional (binocular) vision in adult amblyopic rats. We report that visual perceptual learning induced a marked and long-lasting recovery of visual acuity, visual depth perception abilities and binocular matching of orientation preference, and we provide a link between the last two parameters.

Antioxidants Prevent the Effects of Physical Exercise on Visual Cortical Plasticity.

BACKGROUND: Physical activity has been recently shown to enhance adult visual cortical plasticity, both in human subjects and animal models. While physical activity activates mitochondrial oxidative metabolism leading to a transient production of reactive oxygen species, it remains unknown whether this process is involved in the plasticizing effects elicited at the visual cortical level. RESULTS: Here, we investigated whether counteracting oxidative stress through a dietary intervention with antioxidants (vitamins E and C) interferes with the impact of physical exercise on visual cortex plasticity in adult rats. Antioxidant supplementation beyond the closure of the critical period blocked ocular dominance plasticity in response to eye deprivation induced by physical activity in adult rats. CONCLUSIONS: Antioxidants exerted their action through a mithormetic effect that involved dampening of oxidative stress and insulin-like growth factor 1 (IGF-1) signaling in the brain.

Physical Exercise Modulates Brain Physiology Through a Network of Long- and Short-Range Cellular Interactions.

In the last decades, the effects of sedentary lifestyles have emerged as a critical aspect of modern society. Interestingly, recent evidence demonstrated that physical exercise plays an important role not only in maintaining peripheral health but also in the regulation of central nervous system function. Many studies have shown that physical exercise promotes the release of molecules, involved in neuronal survival, differentiation, plasticity and neurogenesis, from several peripheral organs. Thus, aerobic exercise has emerged as an intriguing tool that, on one hand, could serve as a therapeutic protocol for diseases of the nervous system, and on the other hand, could help to unravel potential molecular targets for pharmacological approaches. In the present review, we will summarize the cellular interactions that mediate the effects of physical exercise on brain health, starting from the factors released in myocytes during muscle contraction to the cellular pathways that regulate higher cognitive functions, in both health and disease.

Running towards amblyopia recovery.

Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life which is a major cause of impaired vision in infants and young children (prevalence around 3.5%). Current treatments such as eye patching are ineffective in a large number of patients, especially when applied after the juvenile critical period. Physical exercise has been recently shown to enhance adult visual cortical plasticity and to promote visual acuity recovery. With the aim to understand the potentialities for translational applications, we investigated the effects of voluntary physical activity on recovery of depth perception in adult amblyopic rats with unrestricted binocular vision; visual acuity recovery was also assessed. We report that three weeks of voluntary physical activity (free running) induced a marked and long-lasting recovery of both depth perception and visual acuity. In the primary visual cortex, ocular dominance recovered both for excitatory and inhibitory cells and was linked to activation of a specific intracortical GABAergic circuit.