• ambliopia
• attività motoria volontaria
• plasticità cerebrale
• ratti

Neural plasticity is defined as the capacity of neural circuits to reorganize structurally and functionally in response to experience. In the sensory systems, well-defined temporal windows early in life can be identified, called critical periods, during which brain circuits are particularly susceptible to the instructive and adaptive signals from the surrounding environment.
The visual system has long been used as the prime model to investigate experience-dependent plasticity. Already in the early 1960s, Hubel and Wiesel demonstrated that occluding one eye in developing mammals with binocular vision (monocular deprivation, DM) induces a dramatic decrease in the proportion of cortical neurons driven by the deprived eye in favour of the non-deprived eye and a reduction of binocular neurons. Since then, DM has become one of the most exploited tools to probe cortical circuit plasticity.
When visual functions mature up to their adult-like levels and the critical period for plasticity in the primary visual cortex (V1) closes, the possibility to induce further functional and anatomical changes by manipulating sensory experience abruptly wanes, due to the maturation of enduring brakes that limit the potential for functional rehabilitation from defective developmental processes. A paradigmatic example is that of amblyopia. Amblyopia (lazy eye) is a neurodevelopmental disorder arising from an early functional imbalance between the two eyes owing to anisometropia, strabismus or congenital monocular cataract. In animal models, this condition can be easily induced by imposing a long-term occlusion of vision through one eye by an enduring DM procedure starting early in the critical period, at postnatal day 21 in rodents, and protracted until adulthood. If not rapidly corrected through proper visual penalization strategies of the healthy eye, it results in the permanent degradation of visual acuity, depth perception and contrast sensitivity. Amblyopia has an estimated incidence of 1-5% in the total population and constitutes the most common cause of monocular visual loss in children, thus being of great clinical and societal importance. This condition is also of a more general interest, as it represents a paradigmatic model for studying how normal brain function gets disrupted as consequence of atypical development and how brain plasticity may be exploited for the recovery of lost function.
While amblyopia has been traditionally considered untreatable after the closure of the critical period, when the brain lacks sufficient plasticity for reinstating proper connections from the affected eye, recent research has challenged the critical period dogma, revealing the possibility to uncover a previously unsuspected potential for plasticity even in the mature brain. Exposure to stimulating environmental conditions (environmental enrichment, EE) promotes a marked recovery of visual functions in adult amblyopic rats subjected to reverse occlusion (i.e. reopening of the long-term deprived eye and closure of the fellow eye), as it enhances visual cortical plasticity acting primarily through a reduction of GABAergic inhibition levels in V1. Strikingly, individual EE components, such as voluntary physical exercise, were also shown to be very effective in promoting recovery of visual acuity and binocularity in adult amblyopic animals.
Given its totally non-invasive nature, physical exercise has a great potential for application to human subjects. However, several open questions remain that should be addressed in order to strengthen the translational applicability of the achieved results:
i) Is it possible to induce recovery of visual function in adult amblyopic animals in binocular conditions (i.e. without reverse occlusion)? ii) Which is the impact of physical exercise on stereopsis abilities in amblyopic animals? iii) Are the benefits on visual recovery persistent? iv) Are all subpopulations of inhibitory interneurons involved at the same extent in the reinstatement of cortical plasticity elicited by physical training?
The present thesis aims to address all these issues using a rat model of amblyopia. Different experimental groups of amblyopic adult rats will be subjected to enhanced voluntary physical training. Visual acuity and stereopsis will be then evaluated at the behavioral level, using the Prusky Water Maze and the visual cliff exploration test respectively. To assess the persistency of the beneficial effects of the employed training protocol, a series of follow-ups will be also performed. Moreover, in order to investigate the specific role of distinct subpopulations of inhibitory interneurons in the reinstatement of visual cortical plasticity, I shall carry out an immunohistochemical experiment where the visual cortex contralateral to the long-term deprived eye will be stained with a double labelling protocol for either one of the two peptides characterizing two of the major sub-populations of GABAergic inhibitory interneurons, namely Vasoactive Intestinal Peptide (VIP) and Somatostatin (SST), and the transcription factor c-Fos, an activity marker classically used as a proxy for neuronal activation levels.