Neural mechanisms of recovery following early visual deprivation

Abstract

Natural patterned early visual input is essential for the normal development of the central visual pathways and the visual capacities they sustain. Without visual input, the functional development of the visual system stalls not far from the state at birth, and if input is distorted or biased the visual system develops in an abnormal fashion resulting in specific visual deficits. Monocular deprivation, an extreme form of biased exposure, results in large anatomical and physiological changes in terms of territory innervated by the two eyes in primary visual cortex (V1) and to a loss of vision in the deprived eye reminiscent of that in human deprivation amblyopia. We review work that points to a special role for binocular visual input in the development of V1 and vision. Our unique approach has been to provide animals with mixed visual input each day, which consists of episodes of normal and biased (monocular) exposures. Short periods of concordant binocular input, if continuous, can offset much longer episodes of monocular deprivation to allow normal development of V1 and prevent amblyopia. Studies of animal models of patching therapy for amblyopia reveal that the benefits are both heightened and prolonged by daily episodes of binocular exposure.

Figure 1

Representation of the daily visual experience of kittens in the form of 24 hours clocks. For four weeks from four weeks of age, kittens received 7 hours of visual experience each day, split between periods of monocular (ME) and binocular (BE) exposure. For the remainder of each day, the kittens were housed in complete darkness (shaded black). The key rearing conditions that were explored include situations where the period of (a) ME preceded or (b) followed BE, conditions where (c) the period of BE was split into two equal intervals that straddled ME and (d) finally situations where the kittens wore masks during the daily period of BE that contained prisms that either had the same orientation for the two eyes (base down or base up) to allow concordant binocular input, or else the opposite orientations so that the visual input was discordant (D). A second cohort of kittens received just 3.5 hours of visual exposure each day.

Figure 2

The visual acuity of the DE (relative to the mean acuity of the NE) measured at the end of the four weeks of mixed daily visual exposure for the two cohorts of kittens as a function of the amount of daily binocular exposure (BE) (a) 7 hours and (b) 3.5 hours. Filled circles depict the animals that received no BE, while the remaining circles show the data from animals that received mixed daily visual input. The half-filled circles are shaded on the left or the right according to whether the period of ME occurred before or after the period of BE, respectively. The open circles show the data from two animals that wore dissociating prisms during the daily period of BE to prevent concordant binocular visual input.

Figure 3

Ocular dominance maps in the primary visual cortex of cats subjected to selective rearing consisting of daily monocular and binocular exposure periods. Each of the three kittens shown had 7 hours of total daily visual exposure, of which different amounts were binocular exposure (BE), as indicated above each maps. Percentages give the amount of cortical territory averaged across both hemispheres that were dominated by the DE. Each map shows the left cortical hemisphere on the left, the right hemisphere on the right, separated by the inter-hemispheric cleft. The top row (a(i)–(iii)) of maps shows as dark patches the regions of visual cortex responding to stimulation of the DE (the left eye in this case). The bottom row of maps (b(i)–(iii)) shows as dark patches the regions of visual cortex responding to stimulation of the NE (the right eye in this case). (i) DE activity patches are very sparse in the absence of any BE, (ii) they are reduced compared with the NE at 0. 5 hours BE, (iii) but close to normal at 1 hours BE per day.

Figure 4

DE territory in V1. The relative cortical area (averaged across both cortical hemispheres) dominated by the DE in each animal is plotted against the daily amount of binocular exposure. Cortical area is normalized relative to the value expected for normal rearing which is set to 100 per cent. Data from the cohort of animals that received a total of 7 hours visual exposure per day are represented by circles and those from the 3.5 hours cohort by squares. The shading of symbols indicates whether binocular experience preceded or followed monocular deprivation (filled squares, 3.5 hours BE before ME; open squares, 3.5 hours BE after ME; filled circles, 7 hours BE before ME; open circles, 7 hours BE after ME). There was no significant effect of the sequence of daily visual experience in either the 3.5 hours cohort or the 7 hours cohort. All data represent mean ±1 s.e.m. An exponential function, described by the equation f(t)=−70.70e^−1.824t+99.02, is fitted to the combined data (dotted line).