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Papers by Donald Mitchell

Research paper thumbnail of Short periods of concordant binocular vision prevent the development of deprivation amblyopia

European Journal of Neuroscience, May 1, 2006

Research paper thumbnail of Documentation of the Development of Various Visuomotor Responses in Typically Reared Kittens and Those Reared With Early Selected Visual Exposure by Use of a New Procedure

Frontiers in Neuroscience

A new procedure was used to study the development of gaze (responses to moving targets or laser s... more A new procedure was used to study the development of gaze (responses to moving targets or laser spots in normal kittens, those that had been reared in total darkness to 6 weeks of age, and others that received a period of monocular deprivation (MD). Gaze responses were observed to all stimuli in normal kittens at between 25–30 days of age and striking responses occurred on the same day or the next. Despite slow acquisition of spatial vision in the dark reared kittens over 3 months, they were able to follow and even strike at moving visual stimuli within a day of their initial exposure to light. By contrast, for a week following a period of MD, kittens showed no gaze or striking responses to moving stimuli when using their previously deprived eye. The very different profiles of acquisition of visuomotor skills and spatial vision in visually deprived kittens point to a dissociation between the neuronal populations that support these functions.

Research paper thumbnail of Environmental Modification of the Visual Cortex and the Neural Basis of Learning and Memory

Research paper thumbnail of The effects of dark-rearing on visual callosal connections of cats

Brain Research, May 1, 1979

Callosal axons ramify along the 17-18 border, in normal cats distributing mainly in that part of ... more Callosal axons ramify along the 17-18 border, in normal cats distributing mainly in that part of area 17 on which is represented the central 2 ° of the visual field t-3,5, 7-9. In Siamese cats and in regular cats with surgically induced squint, axons from the corpus callosum spread further from the 17-18 border than normal 7-9 indicating that the patterns of callosal projections are not rigidly fixed but depend to some extent on the visuotopic map on area 17. The broader callosal distribution could be the result of an active at tempt by cells receiving input f rom the vertical midline to connect with cells receiving similar visual input. Alternatively, it could reflect the negative result of a failure of a broad connection early in development to focus at the 17-18 border if the cells along that border fail to receive visual input from the vertical midline through both eyes. It is possible to dissociate these two alternative possibilities by examination of the callosal connections of kittens that had been reared in total darkness from birth. I f the broad callosal connections were the result of an active at tempt to interconnect cells responding to stimulation of the vertical midline, then dark-reared cats might show reduced or absent callosal projections: if the connections failed to focus during the course of development then dark-reared cats should have a broader distribution of callosal axons than normal. This was tested in 4 kittens raised in the dark until 127 days, 208 days (2 animals) and 242 days postnatal, respectively. When the animals were removed f rom the dark, all but the 127 day deprived cat showed marked divergent strabismus on casual inspection. After a general examination of visuomotor deficits, the left lateral gyrus was removed and after 4 days survival, the animals were perfused with buffered paraformatdehyde. The brains were cut transversely at 26 #m and sections stained with F ink-Heimer and Nissl stains. Normal kittens aged 173 days and 208 days received similar lesions and together with the strabismic cats reported in the next paper served as controls.

Research paper thumbnail of Squint-induced modification of callosal connections in cats

Brain Research, Apr 1, 1978

A commissural pathway occurs in the frog, Xenopus, which interconnects the two optic tecta 7,9 11... more A commissural pathway occurs in the frog, Xenopus, which interconnects the two optic tecta 7,9 11. It develops late in ontogeny and relates points seeing the same region of the visual field, even though one eye may have been rotated or otherwise manipulated prior to metamorphosis. The role of vision in determining the order of the pathway is demonstrated by the finding that adjustments resulting from eye rotation do not occur in animals reared in the dark 11. An interesting parallel is provided in the mammalian nervous system by the callosal connections between the visual cortical areas of the cat. These appear to connect quite late in ontogeny t (although our unpublished studies find a callosal connection somewhat earlier than indicated by Anker and Craggl), and are modified to accommodate the aberration found in the geniculo-cortical pathway of 'Boston' Siamese cats 14,15. The question arises as to what result might be expected if a squint is induced early in development in regular cats. Any variation from normal would not only bear directly on the frog experiments but also add a complication to interpretation of the Siamese cat studies since these animals apparently exhibited marked strabismus. To test this, regular cats (showing no indication of Siamese traits) were subjected to varying degrees of squint by cutting either lateral or medial rectus muscles, of one or both eyes on postnatal days 9-10 (5 animals-4 divergent, 1 convergent), days 44-56 (2 animals, I divergent, 1 convergent), day 84 (1 animal, divergent) and day 112 (1 animal, divergent). After 4 years survival, a large lesion was made involving one lateral gyrus in these cats, as well as in 4 control animals with normal eye alignment. Four days later the cats were perfused with buffered paraformaldehyde. The brains were subsequently sectioned transversely at 26 /~m and the sections stained by Fink Helmet 5 and Nissl methods. Description is restricted in this paper to the callosal projection to area 17.

Research paper thumbnail of Binocular depth perception and the corpus callosum

Vision Research, 1970

MITCHELL and BLAKEMORE'S finding (1970) that the split-brain human does not have the ability to l... more MITCHELL and BLAKEMORE'S finding (1970) that the split-brain human does not have the ability to localize objects in depth along the midline while still retaining depth perception 5" in the periphery does, indeed, suggest a possible neural substrate for depth perception. Some rather important controls, however, seem to be missing from their article. Although they indicate that "Previous tests on L.B. and other split-brain patients. .. have shown that, although they are unable to make verbal description of stimuli delivered to the right hemisphere, their other motor responses for such stimuli are quite normal", and although they ". .. hoped that the clasped-hand technique would optimize collaboration between the hemispheres in making the response", they have not eliminated the possibility that the midline "chance" performance could have been due to a response deficit. What would L.B.'s "peripheral depth perception" in the left hemisphere have been like had he responded with the "clasped-hand technique", rather than verbally ? And, perhaps more importantly, what would his "peripheral depth perception" in the right hemisphere have been like, had this been tested ? In order to rule out the possibility of a "response deficit" (perhaps as a result of organic brain damage to the right hemisphere (?)), it would seem that one must have measures of "peripheral depth perception" both to the left and right using the same response class as one uses for the midline case. If, then, L.B. responds at the "better than chance" level to the left and to the right and at the "chance" level at the midline, then, and only then, would one be justified in concluding that "interhemispheric fibres in the human corpus callosum are necessary for binocular integration in the center of the visual field". It is most important that Mitchell and Blakemore report if these control procedures were employed, and, if so, what the results were. If not, it seems clear that they must be run in order to clearly state the case for the importance of the interhemispheric connections in midline depth perception.

Research paper thumbnail of Asymmetry in the visual callosal connections of strabismic cats

Brain Research, May 1, 1979

In a previous study it was found that the visual callosal connections were expanded in area 17 of... more In a previous study it was found that the visual callosal connections were expanded in area 17 of cats in which a squint had been surgically induced when youngL In that group of animals, divergent squints had been induced in the left eye alone, and convergent squints by bilateral surgery. The callosal projections were tested in all but one animal by tracing the degeneration produced by large lesions of the left visual cortex. In subsequent experiments we have found that there appears to be asymmetry in the callosal projections of cats with squint induced by unilateral surgery. This was studied by rearing kittens with strabismus induced in the left eye within 2 weeks of birth. At various ages between 150 and 210 days postnatal, a large lesion was made involving either the right or left lateral gyrus. Since these animals were somewhat younger than those previously studied, two normals aged 173 days and 208 days were given similar lesions. Four days after surgery, the animals were perfused with buffered paraformaldehyde and the brains sub3equentty sectioned transversely at 26 #m and stained with Fink-Heimer and Nissl methods. Although the extent of the lesions was not exactly identical in each animal, there was no indication that the variation observed in the distribution of callosal connections could be accounted for by differences in lesion size. The results are summarized diagrammatically in Fig. 1. In an animal with a left divergent squint and a left cortical lesion, the callosal connections were expanded exactly as in cats of the previous study, and coarse degenerating callosal axons were seen extending onto the medial bank of the lateral gyrus as far as the suprasplenial sulcus (Fig. 1A, pathway from left to right; Fig. 2A). In two animals with left divergent squints and right cortical lesions, the callosal projection was near normal or appeared reduced compared with normal (Fig. 1A, right to left; Fig. 2B). There was no indication of any projection along the medial bank of the lateral gyrus. In two cats with a left convergent squint and a left cortical lesion, the degeneration in the normal area of catlosal projection was slightly less than normal and no

Research paper thumbnail of Meridional amblyopia: Evidence for modification of the human visual system by early visual experience

Vision Research, Mar 1, 1973

Research paper thumbnail of Brief daily binocular vision prevents the behavioural and physiological effects of monocular deprivation

Research paper thumbnail of Animal models of amblyopia

Visual Neuroscience, 2018

Cit a tio n fo r fin al p u blis h e d ve r sio n: Mi t c h ell, Do n al d a n d S e n g pi el, F... more Cit a tio n fo r fin al p u blis h e d ve r sio n: Mi t c h ell, Do n al d a n d S e n g pi el, F r a n k 2 0 1 8. Ani m al m o d el s of a m blyo pi a. Vis u al N e u r o s ci e n c e 3 5

Research paper thumbnail of Reply to letter by Steven J. Cool

Vision Research, Jul 1, 1971

Research paper thumbnail of The Site of Orientational Constancy

Perception, Sep 1, 1972

The visual world remains perceptually quite stable during rotation of the head. There is some phy... more The visual world remains perceptually quite stable during rotation of the head. There is some physiological evidence that in the cat this phenomenon of orientational constancy might result from changes in the orientation selectivity of neurones in the visual cortex during head tilt. In humans adaptation to a grating causes elevation of the threshold contrast for detecting gratings of similar orientation, and it can be argued that this aftereffect depends on neurones in the human visual cortex. If the head is tilted during such adaptation, but is vertical when the threshold is tested with a vertical grating, the maximum aftereffect occurs for an adapting grating that was vertical on retinal coordinates. We conclude that in humans the mechanism for orientational constancy occurs after the visual cortex.

Research paper thumbnail of Documentation of the Development of Various Visuomotor Responses in Typically Reared Kittens and Those Reared With Early Selected Visual Exposure by Use of a New Procedure

Frontiers in Neuroscience, 2021

A new procedure was used to study the development of gaze (responses to moving targets or laser s... more A new procedure was used to study the development of gaze (responses to moving targets or laser spots in normal kittens, those that had been reared in total darkness to 6 weeks of age, and others that received a period of monocular deprivation (MD). Gaze responses were observed to all stimuli in normal kittens at between 25–30 days of age and striking responses occurred on the same day or the next. Despite slow acquisition of spatial vision in the dark reared kittens over 3 months, they were able to follow and even strike at moving visual stimuli within a day of their initial exposure to light. By contrast, for a week following a period of MD, kittens showed no gaze or striking responses to moving stimuli when using their previously deprived eye. The very different profiles of acquisition of visuomotor skills and spatial vision in visually deprived kittens point to a dissociation between the neuronal populations that support these functions.

Research paper thumbnail of The critical period for darkness-induced recovery of the vision of the amblyopic eye following early monocular deprivation

Journal of Vision, 2019

Exposure of kittens to complete darkness for 10 days has been shown (Duffy & Mitchell, 2013) to r... more Exposure of kittens to complete darkness for 10 days has been shown (Duffy & Mitchell, 2013) to reverse the loss of visual acuity that follows a prior period of monocular deprivation (MD). In that study, recovery of acuity in the previously deprived eye was fast despite the fact that darkness was imposed 2 months after the period of MD when kittens were 3 months old. In a later study (Holman, Duffy, & Mitchell, 2018), it was demonstrated that the same period of darkness was ineffective when it was imposed on cats about 1 year old, suggesting that dark exposure may only promote recovery when applied within an early critical period. To determine the profile of this critical period, the identical period of darkness (10 days) was imposed on kittens at various ages that had all received the same 7-day period of MD from postnatal day 30 (P30). Recovery of the acuity of the deprived eye as measured by use of a jumping stand was complete when darkness was imposed prior to P186 days, but thereafter, darkness induced progressively smaller acuity improvements and was ineffective in kittens when it began at or beyond P191 days of age. These data indicate a critical period for darkness-induced recovery with an abrupt end over a 5-day period.

Research paper thumbnail of Fast Recovery of the Amblyopic Eye Acuity of Kittens following Brief Exposure to Total Darkness Depends on the Fellow Eye

Neural Plasticity, 2019

Recent studies conducted on kittens have revealed that the reduced visual acuity of the deprived ... more Recent studies conducted on kittens have revealed that the reduced visual acuity of the deprived eye following a short period of monocular deprivation imposed in early life is reversed quickly following a 10-day period spent in total darkness. This study explored the contribution of the fellow eye to the darkness-induced recovery of the acuity of the deprived eye. Upon emergence of kittens from darkness, the fellow eye was occluded for different lengths of time in order to investigate its effects on either the speed or the extent of the recovery of acuity of the deprived eye. Occlusion of the fellow eye for even a day immediately following the period spent in darkness blocked any recovery of the acuity of the deprived eye. Moreover, occlusion of the fellow eye two days after the period of darkness blocked any further visual recovery beyond that achieved in the short period when both eyes were open. The results imply that the darkness-induced recovery of the acuity of the deprived ey...

Research paper thumbnail of Animal models of amblyopia

Visual Neuroscience, 2018

Unquestionably, the last six decades of research on various animal models have advanced our under... more Unquestionably, the last six decades of research on various animal models have advanced our understanding of the mechanisms that underlie the many complex characteristics of amblyopia as well as provided promising new avenues for treatment. While animal models in general have served an important purpose, there nonetheless remain questions regarding the efficacy of particular models considering the differences across animal species, especially when the goal is to provide the foundations for human interventions. Our discussion of these issues culminated in three recommendations for future research to provide cohesion across animals models as well as a fourth recommendation for acceptance of a protocol for the minimum number of steps necessary for the translation of results obtained on particular animal models to human clinical trials. The three recommendations for future research arose from discussions of various issues including the specific results obtained from the use of different...

Research paper thumbnail of Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas

Proceedings of the National Academy of Sciences of the United States of America, Dec 6, 2016

A half-century of research on the consequences of monocular deprivation (MD) in animals has revea... more A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of v...

Research paper thumbnail of Brief daily binocular vision prevents monocular deprivation effects in visual cortex

European Journal of Neuroscience, 2007

Even short periods of early monocular deprivation result in reduced cortical representation and v... more Even short periods of early monocular deprivation result in reduced cortical representation and visual acuity of the deprived eye. However, we have shown recently that the dramatic deprivation effects on vision can be prevented entirely if the animal receives a brief period of concordant binocular vision each day. We examine here the extent to which the cortical deprivation effects can be counteracted by daily periods of normal experience. Cats received variable daily regimens of monocular deprivation (by wearing a mask) and binocular vision. We subsequently assessed visual cortex function with optical imaging of intrinsic signals and visually evoked potential recordings. Regardless of the overall length of visual experience, daily binocular vision for as little as 30 min, but no less, allowed normal ocular dominance and visual responses to be maintained despite several times longer periods of deprivation. Thus, the absolute amount of daily binocular vision rather than its relative ...

Research paper thumbnail of Monocular deprivation reduces reliability of visual cortical responses to binocular disparity stimuli

European Journal of Neuroscience, 2007

While continuous monocular deprivation (MD) of patterned vision causes severe loss of visual cort... more While continuous monocular deprivation (MD) of patterned vision causes severe loss of visual cortical responses and visual acuity in the affected eye, these effects can be avoided by providing brief daily periods of binocular exposure [BE; D.E.

Research paper thumbnail of Haphazard neural connections underlie the visual deficits of cats with strabismic or deprivation amblyopia

European Journal of Neuroscience, 2005

Identification of the neural basis of the visual deficits experienced by humans with amblyopia, p... more Identification of the neural basis of the visual deficits experienced by humans with amblyopia, particularly when associated with strabismus (strabismic amblyopia), has proved to be difficult in part because of the inability to observe directly the neural changes at various levels of the human visual pathway. Much of our knowledge has necessarily been obtained on the basis of sophisticated psychophysical studies as well as from electrophysiological explorations on the visual pathways in animal models of amblyopia. This study combines these two approaches to the problem by employing similar psychophysical probes of performance on animal models of two forms of amblyopia (deprivation and strabismic) to those employed earlier on human amblyopes (Hess & Field, 1994, Vis. Res., 34, 13397–13406). The tests explore two competing explanations for the visual deficits, namely an evenly distributed loss of neural connections (undersampling) with the amblyopic eye as opposed to disordered connec...

Research paper thumbnail of Short periods of concordant binocular vision prevent the development of deprivation amblyopia

European Journal of Neuroscience, May 1, 2006

Research paper thumbnail of Documentation of the Development of Various Visuomotor Responses in Typically Reared Kittens and Those Reared With Early Selected Visual Exposure by Use of a New Procedure

Frontiers in Neuroscience

A new procedure was used to study the development of gaze (responses to moving targets or laser s... more A new procedure was used to study the development of gaze (responses to moving targets or laser spots in normal kittens, those that had been reared in total darkness to 6 weeks of age, and others that received a period of monocular deprivation (MD). Gaze responses were observed to all stimuli in normal kittens at between 25–30 days of age and striking responses occurred on the same day or the next. Despite slow acquisition of spatial vision in the dark reared kittens over 3 months, they were able to follow and even strike at moving visual stimuli within a day of their initial exposure to light. By contrast, for a week following a period of MD, kittens showed no gaze or striking responses to moving stimuli when using their previously deprived eye. The very different profiles of acquisition of visuomotor skills and spatial vision in visually deprived kittens point to a dissociation between the neuronal populations that support these functions.

Research paper thumbnail of Environmental Modification of the Visual Cortex and the Neural Basis of Learning and Memory

Research paper thumbnail of The effects of dark-rearing on visual callosal connections of cats

Brain Research, May 1, 1979

Callosal axons ramify along the 17-18 border, in normal cats distributing mainly in that part of ... more Callosal axons ramify along the 17-18 border, in normal cats distributing mainly in that part of area 17 on which is represented the central 2 ° of the visual field t-3,5, 7-9. In Siamese cats and in regular cats with surgically induced squint, axons from the corpus callosum spread further from the 17-18 border than normal 7-9 indicating that the patterns of callosal projections are not rigidly fixed but depend to some extent on the visuotopic map on area 17. The broader callosal distribution could be the result of an active at tempt by cells receiving input f rom the vertical midline to connect with cells receiving similar visual input. Alternatively, it could reflect the negative result of a failure of a broad connection early in development to focus at the 17-18 border if the cells along that border fail to receive visual input from the vertical midline through both eyes. It is possible to dissociate these two alternative possibilities by examination of the callosal connections of kittens that had been reared in total darkness from birth. I f the broad callosal connections were the result of an active at tempt to interconnect cells responding to stimulation of the vertical midline, then dark-reared cats might show reduced or absent callosal projections: if the connections failed to focus during the course of development then dark-reared cats should have a broader distribution of callosal axons than normal. This was tested in 4 kittens raised in the dark until 127 days, 208 days (2 animals) and 242 days postnatal, respectively. When the animals were removed f rom the dark, all but the 127 day deprived cat showed marked divergent strabismus on casual inspection. After a general examination of visuomotor deficits, the left lateral gyrus was removed and after 4 days survival, the animals were perfused with buffered paraformatdehyde. The brains were cut transversely at 26 #m and sections stained with F ink-Heimer and Nissl stains. Normal kittens aged 173 days and 208 days received similar lesions and together with the strabismic cats reported in the next paper served as controls.

Research paper thumbnail of Squint-induced modification of callosal connections in cats

Brain Research, Apr 1, 1978

A commissural pathway occurs in the frog, Xenopus, which interconnects the two optic tecta 7,9 11... more A commissural pathway occurs in the frog, Xenopus, which interconnects the two optic tecta 7,9 11. It develops late in ontogeny and relates points seeing the same region of the visual field, even though one eye may have been rotated or otherwise manipulated prior to metamorphosis. The role of vision in determining the order of the pathway is demonstrated by the finding that adjustments resulting from eye rotation do not occur in animals reared in the dark 11. An interesting parallel is provided in the mammalian nervous system by the callosal connections between the visual cortical areas of the cat. These appear to connect quite late in ontogeny t (although our unpublished studies find a callosal connection somewhat earlier than indicated by Anker and Craggl), and are modified to accommodate the aberration found in the geniculo-cortical pathway of 'Boston' Siamese cats 14,15. The question arises as to what result might be expected if a squint is induced early in development in regular cats. Any variation from normal would not only bear directly on the frog experiments but also add a complication to interpretation of the Siamese cat studies since these animals apparently exhibited marked strabismus. To test this, regular cats (showing no indication of Siamese traits) were subjected to varying degrees of squint by cutting either lateral or medial rectus muscles, of one or both eyes on postnatal days 9-10 (5 animals-4 divergent, 1 convergent), days 44-56 (2 animals, I divergent, 1 convergent), day 84 (1 animal, divergent) and day 112 (1 animal, divergent). After 4 years survival, a large lesion was made involving one lateral gyrus in these cats, as well as in 4 control animals with normal eye alignment. Four days later the cats were perfused with buffered paraformaldehyde. The brains were subsequently sectioned transversely at 26 /~m and the sections stained by Fink Helmet 5 and Nissl methods. Description is restricted in this paper to the callosal projection to area 17.

Research paper thumbnail of Binocular depth perception and the corpus callosum

Vision Research, 1970

MITCHELL and BLAKEMORE'S finding (1970) that the split-brain human does not have the ability to l... more MITCHELL and BLAKEMORE'S finding (1970) that the split-brain human does not have the ability to localize objects in depth along the midline while still retaining depth perception 5" in the periphery does, indeed, suggest a possible neural substrate for depth perception. Some rather important controls, however, seem to be missing from their article. Although they indicate that "Previous tests on L.B. and other split-brain patients. .. have shown that, although they are unable to make verbal description of stimuli delivered to the right hemisphere, their other motor responses for such stimuli are quite normal", and although they ". .. hoped that the clasped-hand technique would optimize collaboration between the hemispheres in making the response", they have not eliminated the possibility that the midline "chance" performance could have been due to a response deficit. What would L.B.'s "peripheral depth perception" in the left hemisphere have been like had he responded with the "clasped-hand technique", rather than verbally ? And, perhaps more importantly, what would his "peripheral depth perception" in the right hemisphere have been like, had this been tested ? In order to rule out the possibility of a "response deficit" (perhaps as a result of organic brain damage to the right hemisphere (?)), it would seem that one must have measures of "peripheral depth perception" both to the left and right using the same response class as one uses for the midline case. If, then, L.B. responds at the "better than chance" level to the left and to the right and at the "chance" level at the midline, then, and only then, would one be justified in concluding that "interhemispheric fibres in the human corpus callosum are necessary for binocular integration in the center of the visual field". It is most important that Mitchell and Blakemore report if these control procedures were employed, and, if so, what the results were. If not, it seems clear that they must be run in order to clearly state the case for the importance of the interhemispheric connections in midline depth perception.

Research paper thumbnail of Asymmetry in the visual callosal connections of strabismic cats

Brain Research, May 1, 1979

In a previous study it was found that the visual callosal connections were expanded in area 17 of... more In a previous study it was found that the visual callosal connections were expanded in area 17 of cats in which a squint had been surgically induced when youngL In that group of animals, divergent squints had been induced in the left eye alone, and convergent squints by bilateral surgery. The callosal projections were tested in all but one animal by tracing the degeneration produced by large lesions of the left visual cortex. In subsequent experiments we have found that there appears to be asymmetry in the callosal projections of cats with squint induced by unilateral surgery. This was studied by rearing kittens with strabismus induced in the left eye within 2 weeks of birth. At various ages between 150 and 210 days postnatal, a large lesion was made involving either the right or left lateral gyrus. Since these animals were somewhat younger than those previously studied, two normals aged 173 days and 208 days were given similar lesions. Four days after surgery, the animals were perfused with buffered paraformaldehyde and the brains sub3equentty sectioned transversely at 26 #m and stained with Fink-Heimer and Nissl methods. Although the extent of the lesions was not exactly identical in each animal, there was no indication that the variation observed in the distribution of callosal connections could be accounted for by differences in lesion size. The results are summarized diagrammatically in Fig. 1. In an animal with a left divergent squint and a left cortical lesion, the callosal connections were expanded exactly as in cats of the previous study, and coarse degenerating callosal axons were seen extending onto the medial bank of the lateral gyrus as far as the suprasplenial sulcus (Fig. 1A, pathway from left to right; Fig. 2A). In two animals with left divergent squints and right cortical lesions, the callosal projection was near normal or appeared reduced compared with normal (Fig. 1A, right to left; Fig. 2B). There was no indication of any projection along the medial bank of the lateral gyrus. In two cats with a left convergent squint and a left cortical lesion, the degeneration in the normal area of catlosal projection was slightly less than normal and no

Research paper thumbnail of Meridional amblyopia: Evidence for modification of the human visual system by early visual experience

Vision Research, Mar 1, 1973

Research paper thumbnail of Brief daily binocular vision prevents the behavioural and physiological effects of monocular deprivation

Research paper thumbnail of Animal models of amblyopia

Visual Neuroscience, 2018

Cit a tio n fo r fin al p u blis h e d ve r sio n: Mi t c h ell, Do n al d a n d S e n g pi el, F... more Cit a tio n fo r fin al p u blis h e d ve r sio n: Mi t c h ell, Do n al d a n d S e n g pi el, F r a n k 2 0 1 8. Ani m al m o d el s of a m blyo pi a. Vis u al N e u r o s ci e n c e 3 5

Research paper thumbnail of Reply to letter by Steven J. Cool

Vision Research, Jul 1, 1971

Research paper thumbnail of The Site of Orientational Constancy

Perception, Sep 1, 1972

The visual world remains perceptually quite stable during rotation of the head. There is some phy... more The visual world remains perceptually quite stable during rotation of the head. There is some physiological evidence that in the cat this phenomenon of orientational constancy might result from changes in the orientation selectivity of neurones in the visual cortex during head tilt. In humans adaptation to a grating causes elevation of the threshold contrast for detecting gratings of similar orientation, and it can be argued that this aftereffect depends on neurones in the human visual cortex. If the head is tilted during such adaptation, but is vertical when the threshold is tested with a vertical grating, the maximum aftereffect occurs for an adapting grating that was vertical on retinal coordinates. We conclude that in humans the mechanism for orientational constancy occurs after the visual cortex.

Research paper thumbnail of Documentation of the Development of Various Visuomotor Responses in Typically Reared Kittens and Those Reared With Early Selected Visual Exposure by Use of a New Procedure

Frontiers in Neuroscience, 2021

A new procedure was used to study the development of gaze (responses to moving targets or laser s... more A new procedure was used to study the development of gaze (responses to moving targets or laser spots in normal kittens, those that had been reared in total darkness to 6 weeks of age, and others that received a period of monocular deprivation (MD). Gaze responses were observed to all stimuli in normal kittens at between 25–30 days of age and striking responses occurred on the same day or the next. Despite slow acquisition of spatial vision in the dark reared kittens over 3 months, they were able to follow and even strike at moving visual stimuli within a day of their initial exposure to light. By contrast, for a week following a period of MD, kittens showed no gaze or striking responses to moving stimuli when using their previously deprived eye. The very different profiles of acquisition of visuomotor skills and spatial vision in visually deprived kittens point to a dissociation between the neuronal populations that support these functions.

Research paper thumbnail of The critical period for darkness-induced recovery of the vision of the amblyopic eye following early monocular deprivation

Journal of Vision, 2019

Exposure of kittens to complete darkness for 10 days has been shown (Duffy & Mitchell, 2013) to r... more Exposure of kittens to complete darkness for 10 days has been shown (Duffy & Mitchell, 2013) to reverse the loss of visual acuity that follows a prior period of monocular deprivation (MD). In that study, recovery of acuity in the previously deprived eye was fast despite the fact that darkness was imposed 2 months after the period of MD when kittens were 3 months old. In a later study (Holman, Duffy, & Mitchell, 2018), it was demonstrated that the same period of darkness was ineffective when it was imposed on cats about 1 year old, suggesting that dark exposure may only promote recovery when applied within an early critical period. To determine the profile of this critical period, the identical period of darkness (10 days) was imposed on kittens at various ages that had all received the same 7-day period of MD from postnatal day 30 (P30). Recovery of the acuity of the deprived eye as measured by use of a jumping stand was complete when darkness was imposed prior to P186 days, but thereafter, darkness induced progressively smaller acuity improvements and was ineffective in kittens when it began at or beyond P191 days of age. These data indicate a critical period for darkness-induced recovery with an abrupt end over a 5-day period.

Research paper thumbnail of Fast Recovery of the Amblyopic Eye Acuity of Kittens following Brief Exposure to Total Darkness Depends on the Fellow Eye

Neural Plasticity, 2019

Recent studies conducted on kittens have revealed that the reduced visual acuity of the deprived ... more Recent studies conducted on kittens have revealed that the reduced visual acuity of the deprived eye following a short period of monocular deprivation imposed in early life is reversed quickly following a 10-day period spent in total darkness. This study explored the contribution of the fellow eye to the darkness-induced recovery of the acuity of the deprived eye. Upon emergence of kittens from darkness, the fellow eye was occluded for different lengths of time in order to investigate its effects on either the speed or the extent of the recovery of acuity of the deprived eye. Occlusion of the fellow eye for even a day immediately following the period spent in darkness blocked any recovery of the acuity of the deprived eye. Moreover, occlusion of the fellow eye two days after the period of darkness blocked any further visual recovery beyond that achieved in the short period when both eyes were open. The results imply that the darkness-induced recovery of the acuity of the deprived ey...

Research paper thumbnail of Animal models of amblyopia

Visual Neuroscience, 2018

Unquestionably, the last six decades of research on various animal models have advanced our under... more Unquestionably, the last six decades of research on various animal models have advanced our understanding of the mechanisms that underlie the many complex characteristics of amblyopia as well as provided promising new avenues for treatment. While animal models in general have served an important purpose, there nonetheless remain questions regarding the efficacy of particular models considering the differences across animal species, especially when the goal is to provide the foundations for human interventions. Our discussion of these issues culminated in three recommendations for future research to provide cohesion across animals models as well as a fourth recommendation for acceptance of a protocol for the minimum number of steps necessary for the translation of results obtained on particular animal models to human clinical trials. The three recommendations for future research arose from discussions of various issues including the specific results obtained from the use of different...

Research paper thumbnail of Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas

Proceedings of the National Academy of Sciences of the United States of America, Dec 6, 2016

A half-century of research on the consequences of monocular deprivation (MD) in animals has revea... more A half-century of research on the consequences of monocular deprivation (MD) in animals has revealed a great deal about the pathophysiology of amblyopia. MD initiates synaptic changes in the visual cortex that reduce acuity and binocular vision by causing neurons to lose responsiveness to the deprived eye. However, much less is known about how deprivation-induced synaptic modifications can be reversed to restore normal visual function. One theoretically motivated hypothesis is that a period of inactivity can reduce the threshold for synaptic potentiation such that subsequent visual experience promotes synaptic strengthening and increased responsiveness in the visual cortex. Here we have reduced this idea to practice in two species. In young mice, we show that the otherwise stable loss of cortical responsiveness caused by MD is reversed when binocular visual experience follows temporary anesthetic inactivation of the retinas. In 3-mo-old kittens, we show that a severe impairment of v...

Research paper thumbnail of Brief daily binocular vision prevents monocular deprivation effects in visual cortex

European Journal of Neuroscience, 2007

Even short periods of early monocular deprivation result in reduced cortical representation and v... more Even short periods of early monocular deprivation result in reduced cortical representation and visual acuity of the deprived eye. However, we have shown recently that the dramatic deprivation effects on vision can be prevented entirely if the animal receives a brief period of concordant binocular vision each day. We examine here the extent to which the cortical deprivation effects can be counteracted by daily periods of normal experience. Cats received variable daily regimens of monocular deprivation (by wearing a mask) and binocular vision. We subsequently assessed visual cortex function with optical imaging of intrinsic signals and visually evoked potential recordings. Regardless of the overall length of visual experience, daily binocular vision for as little as 30 min, but no less, allowed normal ocular dominance and visual responses to be maintained despite several times longer periods of deprivation. Thus, the absolute amount of daily binocular vision rather than its relative ...

Research paper thumbnail of Monocular deprivation reduces reliability of visual cortical responses to binocular disparity stimuli

European Journal of Neuroscience, 2007

While continuous monocular deprivation (MD) of patterned vision causes severe loss of visual cort... more While continuous monocular deprivation (MD) of patterned vision causes severe loss of visual cortical responses and visual acuity in the affected eye, these effects can be avoided by providing brief daily periods of binocular exposure [BE; D.E.

Research paper thumbnail of Haphazard neural connections underlie the visual deficits of cats with strabismic or deprivation amblyopia

European Journal of Neuroscience, 2005

Identification of the neural basis of the visual deficits experienced by humans with amblyopia, p... more Identification of the neural basis of the visual deficits experienced by humans with amblyopia, particularly when associated with strabismus (strabismic amblyopia), has proved to be difficult in part because of the inability to observe directly the neural changes at various levels of the human visual pathway. Much of our knowledge has necessarily been obtained on the basis of sophisticated psychophysical studies as well as from electrophysiological explorations on the visual pathways in animal models of amblyopia. This study combines these two approaches to the problem by employing similar psychophysical probes of performance on animal models of two forms of amblyopia (deprivation and strabismic) to those employed earlier on human amblyopes (Hess & Field, 1994, Vis. Res., 34, 13397–13406). The tests explore two competing explanations for the visual deficits, namely an evenly distributed loss of neural connections (undersampling) with the amblyopic eye as opposed to disordered connec...