Effects of monocular occlusion and diffusion on visual system development in the cat

The effects of two forms of monocular deprivation (occlusion or diffusion) on visual system development were investigated. One group of cats monocularly deprived of all form stimulation but permitted diffuse light stimulation (diffusion, n = 4) during development showed a pattern of deficits similar to those reported for monocularly sutured cats. Most cells in the visual cortex were driven exclusively by the non-deprived eye and there were eye-specific deficits in X-cell acuity, proportion of Y-cells, and cell body size (binocular and monocular segment) in the lateral geniculate nucleus (LGN). A second group of cats monocularly deprived of all form and light stimulation (occlusion, n = 4) during development showed a less severe pattern of deficits. There was no acuity loss in LGN X-cells driven by the deprived eye, and cell body shrinkage was of smaller magnitude than in diffusion reared cats and was restricted to the binocular segment. Cortical deficits and LGN Y-cell loss were similar in the two groups. The results are consistent with the idea that monocular occlusion produces only deficits due to binocular competition while monocular diffusion reflects the combined effects of binocular competition and abnormal stimulation.     

Effects of early monocular deprivation on choline acetyltransferase and glutamic acid decarboxylase in pigeon visual Wulst

Choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities were measured in various visual structures of the pigeon brain after long-term monocular deprivation followed by short-term binocular presence or absence of light stimulation. The short-term phase (45 min) was coupled with a 2-deoxyglucose experiment in order to select the adequate brain samples. After monocular deprivation during the first 6–11 months, ChAT activity was higher by 40–60% in the dorsolateral visual Wulst contralateral to the deprived eye, as compared to the other side. In the same structure, animals, either monocularly deprived or undeprived and exposed binocularly to environmental light for 45 min, had higher ChAT activities on both sides than those maintained in the dark. Monocular deprivation performed in adult animals did not affect the ChAT activity in visual Wulst. GAD activity was bilaterally decreased in the visual Wulst after early monocular deprivation. These results suggest that early monocular deprivation has an effect on biochemical systems involved in synaptic transmission at selected relays of the visual pathways.     

Visual behavior of monocularly deprived kittens treated with 6-hydroxydopamine

Several investigators have reported that treating the visual cortex with 6-hydroxydopamine (6-OHDA) preserves the ability of a monocularly deprived eye to drive cells in the visual cortex. If 6-OHDA provides useful protection from the effects of monocular deprivation, it should also prevent the behavioral blindness that normally accompanies monocular deprivation. To test this prediction we compared the visual behavior of monocularly deprived kittens pretreated with 6-OHDA with that of kittens similarly deprived, but not drug-treated. Kittens were trained on a visual discrimination task before drug treatment or suture. Starting at about 5 weeks of age the kittens were given 6-OHDA via ventricular cannula, given vehicle solution, or given no treatment at all. At about 6 weeks of age all kittens were monocularly deprived for one week. When the deprived eye was opened at 7 weeks of age, most kittens not receiving 6-OHDA were blind when tested with the deprived eye. In contrast, none of the kittens receiving 6-OHDA intraventricularly were blind when tested with the deprived eye. 6-OHDA had no effect on performance with the non-deprived eye. We conclude that 6-OHDA protects vision through the monocularly deprived eye without impairing vision through the non-deprived eye.     

Optokinetic reflex in squirrel monkeys after long‐term monocular deprivation

Horizontal optokinetic nystagmus (OKN) as well as neuronal response properties in the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system (NOT-DTN) were investigated in three monocularly deprived squirrel monkeys. In two monkeys occlusion of one eye was performed at birth (early) and in the third after 7 weeks (late). In adulthood, in early deprived monkeys monocular horizontal OKN tested through the non-deprived eye was symmetrical and in no way different from normal, i.e. stimulation in the temporonasal and nasotemporal direction elicited equal and robust responses. OKN through the early occluded eye, however, was grossly abnormal with low gain and great variability in the consistency of nasotemporal and temporonasal slow phase eye movements. When in the late deprived monkey the non-deprived eye was occluded a strong spontaneous nystagmus developed despite the deprived eye viewing a stationary pattern. The slow phases were directed from nasal to temporal for the deprived eye. When tested through the non-deprived eye all neuronal responses of the NOT-DTN were normal. The deprived eye's influence on NOT-DTN neurons was extremely weak. No neuron with a moderate or even dominant input from the deprived eye was found after early deprivation. In the late deprived case the deficit was not as severe but still the non-deprived eye was clearly dominating the responses in all neurons tested. Velocity tuning of neurons tested through the non-deprived eye was normal and qualitatively corresponded well to slow phase eye velocity in response to equivalent retinal slip during OKN. Through the early deprived eye, however, velocity tuning was extremely poor. It was somewhat better through the late deprived eye. We suggest that the dramatic deterioration in the optokinetic reflex found after long-term monocular deprivation for the amblyopic eye is probably caused by the almost complete loss of retinal and cortical input driven by that eye to the NOT-DTN. These results are discussed in relation to our previous results in cats and reports in the literature for humans with occlusion amblyopia.     

Period of susceptibility of kitten visual cortex to the effects of monocular deprivation extends beyond six months of age

The duration of the sensitive period of the kitten visual cortex to the effects of monocular deprivation was explored by studies of the behavioral and physiological recovery from extended periods of monocular occlusion imposed from birth, and by examination of the physiological effects of a 3 month period of monocular occlusion imposed on animals at either 4, 5, 6, 7 or 8 months of age. Animals monocularly deprived until 4 months of age eventually show considerable behavioral and physiological recovery from the severe deficits observed immediately following termination of the period of deprivation. The conclusion that binocular connectivity may still be altered by the nature of the animal's visual input beyond 4 months of age was supported by the results obtain from animals that were monocularly deprived at 4 months of age or older. Animals deprived at either 4, 5, or 6 months showed a clear shift ocular dominance in favour of the non-deprived eye, but those deprived at 7 or 8 months showed approximately normal ocular dominance distributions. It is concluded that the sensitive period lasts at least twice as long as previously thought, to between 6 and 8 months of age.     

Monocular and binocular deprivation in the monkey: morphological effects and reversibility

Measurements were made of the cross-sectional area of neurons in the lateral geniculate nucleus (LGN) of normal monkeys, and of monkeys subjected to monocular and binocular eyelid suture. Early monocular deprivation caused a failure of normal cell growth in the LGN such that the neurons in the laminae innervated by the deprived eye were, on average, 15% smaller than those innervated by the normal eye. In the first 4 days of life monocular deprivation caused significant retardation of growth. The effect was marked in the first 6 weeks, but was not found in a monkey monocularly deprived from 11-16 months of age nor in an adult deprived for more than 6 months. Binocular deprivation from birth appeared to arrest neuronal growth at the neonatal size. The effect of monocular deprivation could be cancelled by 'reverse-suture' (opening the closed eye and closing the other) during the first 2 months of life. Changes in the size of LGN neurons following monocular deprivation and reverse-suture correlated closely with changes in the relative width of ocular dominance columns in layer IVc of area 17 of the visual cortex, measured physiologically in the same animals.     

Peripheral vision and optokinetic nystagmus in children with unilateral congenital cataract

The vision of cats which were monocularly deprived during early infancy, of kittens, and of young human infants shares two limitations: detection in the nasal visual field is far poorer than detection in the temporal visual field, and optokinetic nystagmus (OKN) is difficult to elicit when a pattern moves nasally to temporally.Here we report similar limitations on the vision of children who had a dense central cataract in one eye during early infancy. Extensive static perimetry with one of these children whose visual acuity was good in both eyes revealed that her threshold for detection all along the horizontal meridian was higher in her aphakic than in her normal eye, with this difference much more pronounced in the nasal visual field than in the temporal visual field. Three children who developed cataracts after 6 months of age showed no such discrepancy between thresholds in the temporal and nasal fields.We tested the symmetry of OKN in 12 children treated for unilateral congenital cataract. In every test of an aphakic (n = 4) or normal eye (n = 12), OKN occurred significantly more often when stripes moved temporally to nasally than when they moved nasally to temporally. In contrast, no asymmetry was observed in any of 13 children treated for traumatic cataracts incurred after 3 years of age.We conclude that children treated for unilateral congenital cataract, like young human infants and monocularly deprived cats, show asymmetric OKN and relatively poor detection in the nasal visual field.     

Ocular dominance of cortical cells in cats dark-reared into maturity after short postnatal monocular deprivation

We studied the preservation of the early monocular deprivation effect by rearing kittens in complete darkness for long periods (9.5 to 20 months) after a monocular deprivation period of 4 weeks that was initiated at the age of 1 month (MDDR cats). For comparison, four groups of kittens were used: monocularly deprived as those described above and then reared in normal light conditions (MDN), monocularly deprived at the age of 1 month (MD), and dark-reared (DR) or normally light-reared (NOR) from birth. Recordings from the visual cortex of MDDR and MDN cats showed that there was a clear preference for cells driven only by the experienced eye compared with the deprived eye. This preference was found whether, subsequent to the monocular deprivation period, these cats were dark- or light-reared (P less than 0.005 for MDDR and MDN compared with NOR cats). The difference between the MDDR, MDN, and MD groups of cats was reflected in the proportions of binocularly driven cells; the largest number of binocularly driven cells was found in the MDDR cats. There was no bias toward either eye in the ocular dominance distribution of cortical cells in cats that were reared in total darkness (DR) or in the light under normal conditions (NOR). We thus conclude that the long-term dark period during development did not erase the effect of early monocular deprivation on the cat visual cortex provided that the latter lasted 4 weeks prior to the dark period.     

Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats.

The hypothesis that NGF could play a role in the plasticity of the developing mammalian visual cortex was tested in monocularly deprived (MD) rats. In particular, we have asked whether an exogenous supply of NGF could prevent the changes in ocular dominance distribution induced by monocular deprivation. Hooded rats were monocularly deprived for 1 month, starting at postnatal day 14 (P14), immediately before eye opening, by means of eyelid suture. In eight rats, only monocular deprivation was performed; in eight rats, monocular deprivation was combined with intraventricular injections of beta-NGF, and in three rats, with intraventricular injections of cytochrome C. Injections (2 microliters) were given every other day for a period of 1 month. Single neuron activity was recorded in the primary visual cortex of MD rats, MD rats treated with NGF, and MD rats treated with cytochrome C at the end of the deprivation period, and in normal rats of the same age. We found that monocular deprivation caused a striking change in the ocular dominance distribution of untreated MD rats, reducing binocular cells by a factor of two and increasing by a factor of eight the number of cells dominated by the nondeprived eye. In MD NGF-treated rats, the ocular dominance distribution was indistinguishable from the normal. Cytochrome C treatment was completely ineffective in preventing the ocular dominance shift induced by monocular deprivation. To test whether NGF affected cortical physiology or interfered with transmission of visual information, we evaluated in NGF-treated rats the spontaneous discharge and the orientation selectivity. We found these functional properties to be in the normal range. We conclude that NGF is effective in preventing the effects of monocular deprivation in the rat visual cortex and suggest that NGF is a crucial factor in the competitive processes leading to the stabilization of functional geniculocortical connections during the critical period.     

Visual split brain and monocular deprivation in kittens: differentiation between the effects of disuse and of binocular competition in visual cortex cells

To differentiate between the resulting effect of disuse, developmentally induced by deprivation, and the binocular competition effect on cortical cells, visual split brain was performed concurrently with monocular deprivation in kittens. In the experienced hemisphere of the split brain deprived cats (ipsilaterally to the non-deprived eye), there were twice as many visually responsive cortical cells than found in their inexperienced hemisphere (ipsilaterally to the deprived eye); however, these cells were equal in number to that found in the split brain controls. In the monocularly deprived control cats a relation of 3.2 was found between cells driven by the non-deprived and the deprived eye. Visual disuse, therefore, resulting from monocular deprivation, affects cortical cells under complete absence of binocular competition but is greatly enhanced by the latter.     

TrkA activation in the rat visual cortex by antirat trkA IgG prevents the effect of monocular deprivation

It has been recently shown that intraventricular injections of nerve growth factor (NGF) prevent the effects of monocular deprivation in the rat. We have tested the localization and the molecular nature of the NGF receptor(s) responsible for this effect by activating cortical trkA receptors in monocularly deprived rats by cortical infusion of a specific agonist of NGF on trkA, the bivalent antirat trkA IgG (RTA-IgG). TrkA protein was detected by immunoblot in the rat visual cortex during the critical period. Rats were monocularly deprived for 1 week (P21–28) and RTA-IgG or control rabbit IgG were delivered by osmotic minipumps. The effects of monocular deprivation on the ocular dominance of visual cortical neurons were assessed by extracellular single cell recordings. We found that the shift towards the ipsilateral, non-deprived eye was largely prevented by RTA-IgG. Infusion of RTA-IgG combined with antibody that blocks p75^NTR (REX), slightly reduced RTA-IgG effectiveness in preventing monocular deprivation effects. These results suggest that NGF action in visual cortical plasticity is mediated by cortical TrkA receptors with p75^NTR exerting a facilitatory role.     

'Natural' and artificial monocular deprivation effects on thalamic soma sizes in pigeons

The dominance for visual pattern analysis of the left hemisphere in normal pigeons and the concomitant morphological asymmetries in the optic tectum can be attributed to a 'natural' prehatch monocular deprivation of the left eye resulting from an asymmetrical embryonic position within the egg. Using control animals and pigeons which were monocularly deprived for 10 days after hatching, the present study could show that the cellular soma sizes of the nucleus rotundus within the tectofugal visual pathway are modified by light experience depending on the timepoint and direction of lateralized stimulation. Although rotundal cell size is thus ontogenetically modified in an activity-dependent manner, a detailed comparison makes it likely that the mechanisms which govern developmental plasticity of visual pathways differ between birds and mammals.     

Post-critical period plasticity of callosal transfer to visual cortex cells of cats following early conditioning of monocular deprivation and late optic chiasm transection

We studied whether plasticity-induced callosal transfer exists after the critical period for sensitivity of visual cortex cells in kittens postnatally monocularly deprived and in which interocular competition was cancelled by chiasm transection during adulthood. Callosal transfer was studied acutely (n = 3 cats) and chronically (n = 7) following the chiasm transection (OCAMD). For comparison, adult cats in which chiasm transection only was performed (OCA) were also studied acutely (n = 3) and chronically (n = 9). The results were also compared to cats in which monocular deprivation and chiasm transection were simultaneously performed (OCKMD) during development (n = 6) and to normal control cats (n = 18). Unit recording was extracellularly carried out in visual cortex areas 17 and 18 and their boundary region, where the corpus callosum is represented. When no interocular competition was allowed between the non-deprived and the deprived eye via the thalamocortical direct visual pathways on cortical cells, such as in the OCKMD cats, the absolute majority of the cells were ipsilaterally driven, regardless of which hemisphere was studied. Only a minor proportion (4.1%) of the cells had some contralateral input from the non-deprived eye in the hemisphere ipsilateral to the deprived eye, indicating almost no interhemispheric callosal transfer. A slight increase in the proportion of cells callosally driven from the non-deprived eye (9.8%), was found in this hemisphere in cats in which interocular competition was allowed via the direct visual pathways prior to its cancellation by chiasm transection (OCAMD), if studied acutely after the chiasm transection. A remarkable increase in callosal transfer was found in this hemisphere under chronic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Critical periods for effects of monocular deprivation: differences between striate and extrastriate cortex

The critical period of susceptibility to effects of monocular deprivation was compared in striate cortex and the lateral suprasylvian (LS) visual area of cortex. Twenty-three cats received monocular lid suture for a period of 4 weeks beginning at 4, 12, 18, 26, or 35 weeks of age or as adults. Immediately following the deprivation, single cell recordings were carried out in both cortical areas of each cat. Recordings also were made from five normally reared control cats. For both striate and LS cortex, early monocular deprivation had marked effects on neuronal ocular dominance, including an increased percentage of cells dominated by the nondeprived eye, a decreased percentage of cells dominated by the deprived eye, and a decreased percentage of binocularly driven cells. In both cortical areas, these effects were maximal in animals deprived at 4 weeks of age. Both areas then showed similar monotonic declines in effects of the deprivation following onsets from 4 to 18 weeks of age. However, in older animals there were clear differences in the effects of monocular deprivation on LS and striate cortex. In LS cortex, the monotonic decline in effects continued until 26 weeks of age, and no significant abnormalities were present in animals deprived at 26 weeks of age or older. In striate cortex, however, the effects of monocular deprivation remained relatively constant following onsets from 18 to 35 weeks of age, and significant abnormalities in all measures of ocular dominance were present when deprivation was begun as late as 35 weeks of age. Within-animal comparisons indicated that the greater effects of monocular deprivation on striate cortex than on LS cortex were present in every cat deprived at 26 or 35 weeks of age. Neither cortical area showed significant abnormalities following monocular deprivation in adult cats. These results indicate that the critical period for effects of the same regime of monocular deprivation is over sooner in LS cortex (between 18 and 26 weeks of age) than in striate cortex (after 35 weeks of age). This observation has important implications for an understanding of the sites and mechanisms of effects of visual deprivation and the mechanisms that control critical periods of development.     

Effects of strabismus and monocular deprivation on the eye preference of neurons in the visual claustrum of the cat

Visual response properties of neurons in the dorsocaudal claustrum were studied in two cats reared with convergent strabismus and three cats reared with monocular lid-suture. In the normal claustrum, most cells respond about equally well to stimulation of either eye (Sherk and LeVay, '81). In the strabismic animals, there was a partial breakdown of binocularity: most cells remained binocular but were influenced more strongly by one eye (usually the contralateral eye) than the other. The loss of binocularity was less extreme in the claustrum than in area 17 of the same animals. In the monocularly deprived cats, claustral cells responded exclusively to the experienced eye. We interpret the changes observed in the claustrum as reflecting changes in the ocular dominance of cortical inputs to the claustrum, rather than as evidence for plasticity within the claustrum itself. Autoradiography was used to study the return projection from claustrum to cortex in monocular deprivation. The cortical labeling pattern resembled that seen in normal cats. To examine whether this return projection might be involved in reducing cortical responsiveness to the deprived eye, recordings were made from area 17 of a monocularly deprived cat before and after ablation of the ipsilateral claustrum by injection of kainic acid. Following ablation, there was no unmasking of cortical responses to the deprived eye. Thus the cortico-claustral loop does not appear to suppress cortical responses to the deprived eye.     

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 the effects 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. 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.     

Effect of reopening an eye after a period of monocular deprivation on sizes of neurons in the primate lateral geniculate nucleus

Following monocular closure shortly after birth the deprived eye of 4 rhesus monkeys was reopened at different times. Following long-term recovery, cells in the undeprived laminae of the lateral geniculate nucleus of these animals were of normal size and those in the deprived laminae were markedly shrunken. Comparisons with animals monocularly deprived for similar periods indicate, however, that in 3 of these animals the undeprived parvocellular cells would have been markedly hypertrophied at the time of reopening the deprived eye, and in two of the animals, little shrinkage of the deprived parvocellular cells would have occurred by this time. Both undeprived and deprived parvocellular cells have therefore undergone marked shrinkage after the deprived eye had been reopened. The parallel shrinkage of deprived and undeprived parvocellular cells which occurs following closure at birth thus appears to be a consequence of the initial abnormalities produced by monocular closure rather than a direct result of the continuing lack of visual input to one eye.     

Can functional reorganization of area 17 following monocular deprivation be modified by GM1 internal ester treatment?

It has been extensively reported that monocular exposure early in life leads to profound alterations in visual cortical areas, where the majority of cells become responsive only to the stimulation of the normal eye. We have investigated a possible effect of the monosialoganglioside internal ester, termed AGF2, on the neuronal cortical plasticity of the kitten's visual cortex following monocular deprivation. Results indicate that in monocularly deprived kittens treated with ganglioside the ocular dominance shift in favor of the normal eye is partially prevented.     

Depth Perception in Monocularly Deprived Cats Following Part-time Reverse Occlusion

The behavioural effects of an early period of monocular deprivation can be extremely profound. However, it is possible to achieve a high degree of recovery, even to normal levels of visual acuity, by prompt imposition of certain regimes of part-time reverse occlusion where the initially non-deprived eye is occluded for only part of each day in order to allow a daily period of binocular visual exposure. In this paper we report on the depth perception of five monocularly deprived cats that had recovered normal visual acuity in both eyes following imposition of certain of the above occlusion regimes. Although three of the animals exhibited five-to sevenfold superiority of binocular over monocular depth thresholds, subsequent tests made on two of the animals revealed that they were unable to make stereoscopic discriminations with random-dot stereograms. Despite the recovery of normal visual acuity in both eyes, we conclude that these animals recover at best only local stereopsis.     

The visual field in monocularly deprived cats and its permanence

The present study had two primary aims. The first was to determine the extent of the visual field of the deprived eye of a monocularly deprived cat using visual perimetry techniques, since recent reports have been contrary to previous research. The second aim was to determine whether enucleation of the experienced eye of a monocularly deprived cat was associated with any increase in the extent of the visual field of the deprived eye compared to forced usage (reversesuture). The results indicate that the extent of the visual field using the deprived eye is limited to the ipsilateral monocular visual field. Further, enucleation of the experienced eye leads to a rapid expansion of the visual field of the deprived eye to include the entire ipsilateral hemifield which does not occur following reversesuture. Possible reasons for the conflicting reports in the literature are discussed.