Physiological Effects Of Monocular Deprivation Research Articles

Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats.

Deprivation of normal vision early in postnatal development elicits modifications of neural circuitry within the primary visual pathway that can cause a severe and intractable vision impairment (amblyopia). In cats, amblyopia is often modeled with monocular deprivation (MD), a procedure that involves temporarily closing the lids of one eye. Following long-term MD, brief inactivation of the dominant eye's retina can promote recovery from the anatomical and physiological effects of MD. In consideration of retinal inactivation as a viable treatment for amblyopia it is imperative to compare its efficacy against conventional therapy, as well as assess the safety of its administration. In the current study we compared the respective efficacies of retinal inactivation and occlusion of the dominant eye (reverse occlusion) to elicit physiological recovery from a prior long-term MD in cats. Because deprivation of form vision has been associated with development of myopia, we also examined whether ocular axial length or refractive error were altered by a period of retinal inactivation. The results of this study demonstrate that after a period of MD, inactivation of the dominant eye for up to 10 days elicited significant recovery of visually-evoked potentials that was superior to the recovery measured after a comparable duration of reverse occlusion. After monocular retinal inactivation, measurements of ocular axial length and refractive error were not significantly altered from their pre-inactivation values. The rate of body weight gain also was not changed during the period of inactivation, indicating that general well-being was not affected. These results provide evidence that inactivation of the dominant eye after a period of amblyogenic rearing promotes better recovery than eye occlusion, and this recovery was achieved without development of form-deprivation myopia.

Effect of sensory disuse on geniculate afferents to cat visual cortex.

In the kitten, as little as a week of monocular lid suture during early life causes a remarkable remodeling of the geniculocortical projections serving the deprived eye (Antonini & Stryker, 1993a, 1996). While the physiological effects of monocular deprivation have been shown to be due to competitive interactions between the projections serving the two eyes, it is not known whether these morphological changes are due to competitive interactions or to sensory disuse. We addressed this question by analyzing the morphology of geniculocortical arbors in kittens deprived of patterned vision by binocular lid suture for 1 week or 2 weeks ending at 6 weeks of age. Such deprivation would be expected to affect the afferents serving the two eyes equally, giving neither eye a competitive advantage. The arbors were anterogradely filled with Phaseolus lectin iontophoretically injected into lamina A of the lateral geniculate nucleus. The lectin was visualized immunohistochemically, and single geniculocortical arbors were serially reconstructed in three dimensions. Arbors reconstructed in binocularly deprived animals were compared with arbors serving the deprived and nondeprived eye in animals monocularly deprived by lid suture of one eye for a week and with arbors obtained in age-matched normal controls. Geniculocortical arbors in binocularly deprived animals did not suffer the drastic remodeling of the deprived arbors in monocularly deprived animals. Indeed, arbors in binocularly deprived animals were indistinguishable from arbors in normal kittens or nondeprived arbors in short-term monocularly deprived animals. These results support the notion that competitive mechanisms rather than sensory disuse are responsible for gross morphological remodeling of geniculocortical arbors.

The extent of visual recovery from early monocular or binocular visual deprivation in kittens.

1. The rate and extent of recovery of vision was studied in the deprived eye of kittens that had been monocularly deprived from near birth for periods that lasted from 6 weeks to 18 months. Recovery was measured in the two situations, where either both eyes were open following the initial deprivation (binocular recovery), or else the non-deprived eye was occluded so as to force the animal to employ its deprived eye (reverse occlusion). 2. Measurements were made of the visual acuity of the deprived eye for gratings at frequent intervals during recovery by means of a simple behavioural technique. 3. The acuity that the deprived eye eventually attained declined with increasing length of deprivation in a manner that could be approximated by a simple exponential decay. Only minimal visual recovery was observed in animals deprived beyond 1 year of age; only two of six animals recovered sufficient vision to enable measurement of visual acuity. In general, animals that were reverse occluded recovered better vision than did those that had both eyes open during recovery. 4. The recovery of vision in the deprived eye of monocularly deprived kittens was compared to that observed following equivalent periods of two forms of binocular deprivation, namely dark-rearing and binocular eyelid suture. 5. The recovery from the two forms of binocular deprivation was quite different. Whereas the extent of recovery from dark-rearing was considerably greater than that observed after equivalent periods of monocular deprivation, the recovery of a limited sample of cats that were binocularly deprived by eyelid suture was worse. 6. These findings suggest that some plasticity remains in the visual pathways for a longer time than indicated by experiments that examine the physiological effects of monocular deprivation on various visual cortical structures.

Reversal of the physiological effects of monocular deprivation in adult dark-reared cats

If kittens are dark-reared for 4 months and subsequently monocularly sutured, cells in area 17 become dominated by the experienced eye. We now find that (a) the effect of monocular deprivation in adult dark-reared cats can be reversed by suturing the experienced eye and allowing the cat to use the deprived eye, an effect that has previously been shown only in young kittens. (b) The presence of continuous or nearly continuous visual experience during infancy is required for the critical period to exhaust itself — brief periods of visual experience will not suffice.

Dark rearing prolongs physiological but not anatomical plasticity of the cat visual cortex.

Recent studies (Cynader and Mitchell, '80; Mower et al., '81) have shown that total dark rearing prolongs susceptibility to the physiological effects of monocular deprivation (MD) in visual cortex beyond the normal age limits. The present study addressed whether this delayed physiological plasticity is accompanied by delayed anatomical plasticity in the geniculocortical pathway. Ocular dominance (OD) columns as defined by transsynaptic autoradiography following injection of 3H proline into one eye were studied both qualitatively and quantitatively in 17 cats. Compared to normal rearing (N-3), both binocular eyelid suture (N-2) and total dark rearing (N-3) resulted in incomplete segregation of OD columns in area 17. This apparent immaturity after binocular deprivation, however, did not reflect a delayed capacity for development and plasticity. Visual experience after dark rearing produced no marked changes. In cats who experienced MD after dark rearing, injection of either the nondeprived (N-2) or deprived eye (N-3) resulted in a nearly uniform distribution of label throughout layer IV of area 17. The same result occurred with binocular vision after dark rearing (N-1). MD from birth, however, produced expansion of columns from the nondeprived eye (N-1) and contraction of columns from the deprived eye (N-1). MD imposed after 4 months of normal vision resulted in normal OD columns (N-1). Electrophysiological studies revealed a high proportion of binocular cells within layer IV in cats who experienced monocular or binocular vision after dark rearing. Outside of layer IV there were clear environmental effects on OD of single cells in these cats. Measurements of cell sizes in the clateral geniculate nucleus showed shrinkage of cells innervated by the deprived eye when MD was initiated at birth (N-3). MD after dark rearing (N-4) produced no differences in cell sizes. It is concluded that visual input is necessary for the formation of normal OD columns, the critical period for formation and environmental modification of OD columns is limited to early life, and the physiological effects of visual experience after dark rearing reflect changes occurring beyond the geniculocortical pathway.

Behavioral and physiological effects of monocular deprivation: A comparison of rearing with diffusion and occlusion

To compare the effects of monocular deprivation produced by occlusion and diffusion, 9 cats were reared in the dark from birth to 4 weeks of age, when they were brought out for periods of exposure with one eye covered. For 3 cats, the left eye was covered with a white diffuser while the right eye received 8 h of normal patterned exposure (MD/D-8). For 2 cats, the left eye was covered with a black occluder while the right eye was exposed for 8 h (MD/O-8), and for 4 cats, the right eye was covered with a black occluder while the left eye was exposed for 1 h (MD/O-1). Monocular exposure continued until the cats were 3 months old, when they began receiving binocular exposure. For all cats, the visual field of the exposed eye was normal. For the MD/D cats, the field of the pattern-deprived eye was restricted to the monocular crescent, and resembled the fields of monocularly lid-sultured cats. in contrast, for the MD/O cats, the field of the pattern-deprived eye was much larger, extending nearly to the midline. Thus, monocular diffusion produced more restricted visual fields than did monocular occlusion. Preliminary physiological data from the MD/D-8 and MD/O-8 cats showed that more cortical cells responded to stimulation of the pattern-deprived eye in the MD/O-8 cats than in the MD/D-8 cats. Taken together with our earlier results on cats reared with unequal patterned input to the two eyes, these results further suggest that there is a temporal-to-nasal gradient in sensitivity to the effects of an imbalance in stimulation to the two eyes.

The effects of short-term occlusion therapy on reversal of the anatomical and physiological effects of monocular deprivation in the lateral geniculate nucleus and visual cortex of kittens.

The relative efficacy of distributed versus massed reverse occlusion therapy in promoting recovery from the anatomical and physiological effects of monocular deprivation was studied in two experiments performed on kittens raised with one eye occluded from eye-opening until 5 weeks of age. The first experiment explored the effects of different periods (ranging from 0.5 to 4 h) of reverse occlusion imposed daily for 20 days. The second, involving a fixed period of reverse occlusion (20 h), examined recovery with respect to the distribution of that period over a varied number of brief daily sessions. Recovery was assessed in terms of changes in cortical ocular dominance and lateral geniculate cell morphology. Although recovery of both cortical ocular dominance and geniculate cell morphology showed the same overall progression with increasing periods of reverse occlusion, changes were apparent in the lateral geniculate nucleus before changes were evident in cortical ocular dominance. A given period of reverse occlusion was found to be far more effective in promoting recovery when distributed over a number of different exposure sessions than when massed together in just one or two sessions. The data suggest that there is a maximal rate of cortical recovery which is achieved with surprisingly brief daily periods of forced visual exposure of the initially deprived eye.

Organization of visual pathways in normal and visually deprived cats.

Organization of visual pathways in normal and visually deprived cats.

Prolonged sensitivity to monocular deprivation in dark-reared cats.

Prolonged sensitivity to monocular deprivation in dark-reared cats.

Receptive-field properties of different classes of neurons in visual cortex of normal and dark-reared cats.

ArticlesReceptive-field properties of different classes of neurons in visual cortex of normal and dark-reared catsA. G. Leventhal, and H. V. HirschA. G. Leventhal, and H. V. HirschPublished Online:01 Apr 1980https://doi.org/10.1152/jn.1980.43.4.1111MoreSectionsPDF (4 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByDecoding the orientation of contrast edges from MEG evoked and induced responsesNeuroImage, Vol. 180Orientation anisotropies in human primary visual cortex depend on contrastNeuroImage, Vol. 119Visual experience promotes the isotropic representation of orientation preference3 May 2004 | Visual Neuroscience, Vol. 21, No. 01Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF26 September 2003 | Proceedings of the National Academy of Sciences, Vol. 100, No. 21Oblique Effect: A Neural Basis in the Visual CortexBaowang Li, Matthew R. Peterson, and Ralph D. Freeman1 July 2003 | Journal of Neurophysiology, Vol. 90, No. 1Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys1 April 2000 | Nature Neuroscience, Vol. 3, No. 4The nature and origin of orientation specificity in neurons of the visual pathwaysProgress in Neurobiology, Vol. 43, No. 4-5Simulation of visual cortex development under lid-suture conditions: enhancement of response specificity by a reverse-Hebb rule in the absence of spatially patterned inputBiological Cybernetics, Vol. 70, No. 4Effect of the richness of the environment on neurons in cat visual cortex. I. Receptive field propertiesDevelopmental Brain Research, Vol. 53, No. 1Consequences of visual deprivation in the absence of binocular competitive mechanisms in Siamese cat area 17Developmental Brain Research, Vol. 50, No. 1Unilateral visual cortex deafferentation induces changes in receptive field properties of cortical cells in the intact hemisphere of normal and of monocularly deprived catsDevelopmental Brain Research, Vol. 33, No. 2Physiological segregation of geniculo-cortical afferents in the visual cortex of dark-reared catsBrain Research, Vol. 362, No. 2Synapse elimination in the developing visual cortex: a morphometric analysis in normal and dark-reared catsDevelopmental Brain Research, Vol. 22, No. 1Ocular dominance of cortical cells in cats dark-reared into maturity after short postnatal monocular deprivationExperimental Neurology, Vol. 85, No. 3Survival of early monocular deprivation effects in cortical cells of kittens following prolonged dark rearingDevelopmental Brain Research, Vol. 16, No. 1Synaptic characteristics of identified pyramidal and multipolar non-pyramidal neurons in the visual cortex of young and adult rabbits. A quantitative Golgi-electron microscope studyNeuroscience, Vol. 12, No. 4Human orientation discrimination tested with long stimuliVision Research, Vol. 24, No. 2Behavioral and physiological effects of monocular deprivation: A comparison of rearing with diffusion and occlusionBrain Research, Vol. 280, No. 1Receptive field characteristics of neurones in striate cortex of newborn lambs and adult sheepNeuroscience, Vol. 10, No. 2Meridional variations in the line orientation discrimination of the catBehavioural Brain Research, Vol. 9, No. 2Prolonged sensitivity to monocular deprivation in dark-reared cats: Effects of age and visual exposureDevelopmental Brain Research, Vol. 8, No. 2-3Effects of monocular deprivation upon the binocularity of cells in area 18 of cat visual cortexDevelopmental Brain Research, Vol. 8, No. 1Frequency specific effects of stroboscopic rearing in the visual cortex of the rabbitDevelopmental Brain Research, Vol. 7, No. 2-3An oblique effect of spatial summationVision Research, Vol. 23, No. 6Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivationBrain Research, Vol. 250, No. 2Principal components analysis of cells in cat visual cortexBrain Research, Vol. 251, No. 1Plasticity in the kitten's visual cortex: effects of the suppression of visual experience upon the orientational properties of visual cortical cellsDevelopmental Brain Research, Vol. 4, No. 4The Oblique Effects of Pattern and Flicker Sensitivity: Implications for Mixed Physiological Input25 June 2016 | Perception, Vol. 11, No. 4Meridional Differences in Temporal Resolution25 June 2016 | Perception, Vol. 11, No. 1Comparison of the effects of dark rearing and binocular suture on development and plasticity of cat visual cortexBrain Research, Vol. 220, No. 2The critical period for alteration in cortical binocularity resulting from divergent and convergent strabismusDevelopmental Brain Research, Vol. 2, No. 2The effects of dark-rearing on the development and plasticity of the lateral geniculate nucleusDevelopmental Brain Research, Vol. 1, No. 3The influence of eccentricity on receptive field types and orientation selectivity in areas 17 and 18 of the catBrain Research, Vol. 208, No. 1 More from this issue > Volume 43Issue 4April 1980Pages 1111-1132 Copyright & PermissionsCopyright © 1980 the American Physiological Societyhttps://doi.org/10.1152/jn.1980.43.4.1111PubMed7359177History Published online 1 April 1980 Published in print 1 April 1980 Metrics

Postcritical‐period reversal of effects of monocular deprivation on dorsal lateral geniculate cell size in the cat

AbstractIf cats are raised with monocular lid suture, cells in dorsal lateral geniculate (DLG) laminae which receive inputs from the deprived eye are smaller than normal when the animals reach maturity. Previous studies have shown that after a critical period of development, these morphological changes cannot be reversed by closing the initially experienced eye and opening the initially deprived eye (reverse suture). The present experiment investigated whether removal of the experienced eye, a procedure which rapidly reverses some of the physiological effects of monocular deprivation on striate cortex neurons (Kratz et al., '76), also would produce a reversal of the effects of monocular deprivation on DLG cell size. In addition, if a morphological reversal in DLG cell size could be observed, we were interested in knowing its time course relative to the physiological reversal in striate cortex.Nine control kittens were raised with monocular lid suture until they were four to eight months old (group MD). Comparison with a group of six normally reared kittens (group N) showed the usual effects of monocular deprivation on DLG cell size (cross‐sectional area) which have been reported previously; i.e., a marked reduction in cell size in the deprived binocular segments of laminae A and A1, and a smaller reduction in cell size in the deprived monocular segment of lamina A. Ten additional kittens were raised with monocular lid suture until they were four to five months old, at which time the experienced eye was enucleated. Five of these kittens (group MD‐DE‐Immed) were allowed to survive 30 hours after the enucleation. There was no significant difference in DLG cell size between these animals and the MD control animals. The remaining five kittens (group MD‐DE‐3 mo) were allowed to survive three months after enucleation of the experienced eye, and the deprived eye remained closed during this time. In these kittens, cells in the deprived DLG laminae were significantly larger than cells in the deprived laminae of kittens in both the MD‐DE‐Immed and the MD control groups. In addition, they were not significantly different from normal. The increased cell size in the MD‐DE‐3 mo cats was present in the deprived binocular segments of both laminae A and A1, and to a lesser extent in the deprived monocular segment of lamina A. Cell sizes also were measured in the deafferented (initially experienced) laminae of cats in the MD‐DE‐Immed and MD‐DE‐3 mo groups. They showed a slight decrease in size relative to DLG cells in the experienced laminae of MD control cats.These results indicate that deprived DLG cells can resume their growth after the previously defined critical period. Comparisons with previous studies indicate that it is necessary to completely remove the inputs from the experienced eye for the new growth to occur. However, it is not necessary to provide the deprived eye with visual experience. In addition, the increase in deprived DLG cell size occurs sometime after the increase in ability of the deprived eye to drive striate cortex cells (Kratz et al., '76). Thus, the functional recovery of cortical cells precedes the morphological recovery of DLG cells.

The physiological effects of monocular deprivation and their reversal in the monkey's visual cortex.

1. 1127 single units were recorded during oblique penetrations in area 17 of one normal, three monocularly deprived and four reverse sutured monkeys. 2. In all animals most cells outside layer IV c were orientation-selective, and preferred orientation usually shifted from cell to cell in a regular progressive sequence. 3. The presence in layer IV c of non-oriented, monocularly driven units, organized in alternating right-eye and left-eye 'stripes' (LeVay, Hubel & Wiesel, 1975) was confirmed. 4. Early monocular deprivation (2--5 1/2 weeks) caused a strong shift of ocular dominance towards the non-deprived eye. However, even outside layer IV c, neural background and some isolated cells could still be driven from the deprived eye in regularly spaced, narrow columnar regions. In layer IV c the non-deprived eye's stripes were almost three times wider, on average, than the deprived. 5. Later monocular deprivation (11--16 months) had no detectable influence on layer IV c but seemed to cause a small shift in ocular dominance outside IV c. Deprivation for 6 1/4 months in an adult had no such effect. 6. After early reverse suturing (at 5 1/2 weeks) the originally deprived eye gained dominance over cells outside layer IV c just as complete as that originally exercised by the eye that was first non-deprived. 7. The later reverse suturing was delayed, the less effective was recapture by the originally deprived eye. Reversal at 8 weeks led to roughly equal numbers of cells being dominated by each eye; fewer cells became dominated by the newly open eye after reverse suturing at 9 weeks and most of them were non-oriented; reversal at 38 1/2 weeks had no effect. 8. Binocular cells, though rare in reverse sutured animals, always had very similar preferred orientations in the two eyes. The columnar sequences of preferred orientation were not interrupted at the borders of ocular dominance columns. 9. Even within layer IV c there was evidence for re-expansion of physiologically determined ocular dominance stripes. After early reverse suture, stripes for the two eyes became roughly equal in width. Possible mechanisms for these changes are discussed.

Reversal of the physiological effects of monocular deprivation in the kitten's visual cortex.

1. Twenty-three kittens were monocularly deprived of vision until the age of 4, 5, 6 or 7 weeks. Their deprived eyes were then opened, and their experienced eyes shut for a further 3-63 days. After this time physiological recordings were made in the visual cortex, area 17. Three control kittens, monocularly deprived for various periods, showed that at the time of reverse-suturing, few neurones could be influenced at all from the deprived eye. 2. Following reverse-suturing, the initially deprived eye regained control of cortical neurones. This switch of cortical ocular dominance was most rapid following reverse-suturing at the age of 4 weeks. Delaying the age of reverse-suturing reduced the rate and then the extent of the cortical ocular dominance changes. 3. The cortex of reverse-sutured kittens is divided into regions of cells dominated by one eye or the other. The relative sizes of these ocular dominance columns changed during reversed deprivation. The columns devoted to the initially deprived eye were very small in animals reverse-sutured for brief periods, but in animals that underwent longer periods of reversed deprivation, the columns driven by that eye were larger, while those devoted to the initially open eye were smaller. 4. Clear progressions of orientation columns across the cortex were apparent in many of the kittens, but, in contrast to the situation in normal or strabismic kittens, these sequences were disrupted at the borders of eye dominance columns: the cortical representations of orientation and ocular dominance were not independent. 5. Binocular units in these kittens were rather rare, but those that could be found often had dissimilar receptive field properties in the two eyes. Commonly, a cell would have a normal orientation selective receptive field in one eye, and an immature, unselective receptive field in the other. Cells that had orientation selective receptive fields in both eyes often had greatly differing orientation preferences in the two eyes, occasionally by nearly 90 degrees. 6. During the reversal of deprivation effects, the proportion of receptive fields exhibiting mature properties declined in the initially experienced eye, while the proportion increased in the initially deprived eye. Similarly, the average band width of orientation tuning of receptive fields in the initially deprived eye decreased, while that of receptive fields in the initially experienced eye increased. 7. One kitten was reverse-sutured twice, to demonstrate that cortical ocular dominance may be reversed a second time, even after one reversal of ocular dominance. 8. It is suggested that the sensitive period for cortical binocular development consists of two phases. In the first phase, all cortical neurones may be modified by experience, but the rate at which they may be modified decreases with age. In the second phase, an increasing number of cortical neurones becomes fixed in their properties, while those that remain modifiable are as modifiable as they were at the end of the first phase. 9...

Reversal of the physiological effects of monocular deprivation in kittens: further evidence for a sensitive period.

1. It was confirmed that suturing the lids of one eye (monocular deprivation), until only 5 weeks of age, leaves virtually every neurone in the kitten's visual cortex entirely dominated by the other eye. On the other hand, deprivation of both eyes causes no change in the normal ocular dominance of cortical neurones, most cells being clearly binocularly driven.2. Kittens were monocularly deprived until various ages, from 5 to 14 weeks, at which time reverse suturing was performed: the initially deprived right eye was opened and the left eye closed for a further 9 weeks before recording from the visual cortex.3. Reverse suturing at 5 weeks caused a complete switch in ocular dominance: every cell was dominated by the initially deprived right eye. Reverse suturing at 14 weeks, however, had almost no further effect on ocular dominance: most cells were still driven solely by the left eye. Animals reverse sutured at intermediate ages had cortical neurones strongly dominated by one eye or the other, and they were organized into clear columnar groups according to ocular dominance.4. Thus, between 5 weeks and 4 months of age, there is a period of declining sensitivity to both the effects of an initial period of monocular deprivation and the reversal of those effects by reverse suturing.5. The small proportion of binocular cells in reverse sutured kittens (which have never had simultaneous binocular vision) often differed considerably in their receptive field properties in the two eyes. In particular, if the cells were orientation selective in both eyes the two preferred orientations could differ by up to 70 degrees .6. The relative importance of innate and environmental contributions to the properties of cortical cells is discussed.