The visual system exhibits a heightened sensitivity to the quality visual experience during an interval late in development termed the `critical period'. Discordant vision during the critical period is the cause of amblyopia, a prevalent visual disorder in children. Treatment of amblyopia is most effective in children before the close of the critical period. Subsequently, the flexibility with brain circuitry diminishes in adulthood and effective therapy is more difficult. In a mouse model of amblyopia, disrupting normal vision by closing one (monocular deprivation, MD) for the duration of the critical period, but not thereafter, decreases visual acuity and perturbs the normal eye dominance of neurons in visual cortex. The nogo-66 receptor gene (ngr1) is required to close the critical period. In ngr1 mutant mice, plasticity during the critical period is normal, but it is retained in adult mice. Importantly, ngr1 mutant mice spontaneously recover visual acuity in this model of amblyopia. Our overall hypothesis is that recovery of acuity and eye dominance are independent. In the proposed research, we take advantage of this extended critical period in ngr1 mice to identify with location and mechanisms of plasticity that mediate recovery of acuity and eye dominance with a combination of conditional mouse genetics, behavioural assays, electrophysiology, sophisticated repeated in vivo calcium imaging and laser-scanning photostimulation circuit mapping. We will begin to unravel how plasticity within visual circuitry mediates recovery of visual function following early abnormal vision (MD), as well as how this plasticity is restricted to the critical period with these experiments. In addition to improving understanding of how experience-dependent plasticity changes the function of brain circuits, these studies may reveal new avenues for developing therapeutic approaches to treat amblyopia. .
Abnormal vision only during a ?critical period? in childhood induces amblyopia, also known as lazy eye, a disorder comprising several deficits in spatial vision including poor acuity. The proposed research is relevant to public health because knowledge of the neural circuits that mediate recovery of acuity and eye dominance will improve our understanding of targets for therapeutic intervention. Thus, the proposed research is relevant to the mission of the both the NEI to increase understanding of the critical period in order to determine how experience alters connectivity in the developing visual system.
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