Critical period for monocular deprivation in the cat visual cortex.

1. Cats were monocularly deprived for 3 mo starting at 8-9 mo, 12 mo, 15 mo, and several years of age. Single cells were recorded in both visual cortexes of each cat, and the ocular dominance and layer determined for each cell. Ocular dominance histograms were then constructed for layers II/III, IV, and V/VI for each group of animals. 2. There was a statistically significant shift in the ocular dominance for cells in layers II/III and V/VI for the animals deprived between 8-9 and 11-12 mo of age. There was a small but not statistically significant shift for cells in layer IV from the animals deprived between 8-9 and 11-12 mo of age, and for cells in layers V/VI from the animals deprived between 15 and 18 mo of age. There was no noticeable shift in ocular dominance for any other layers in any other group of animals. 3. We conclude that the critical period for monocular deprivation is finally over at approximately 1 yr of age for extragranular layers (layers II, III, V, and VI) in visual cortex of the cat.     

Recovery of function in cat visual cortex following prolonged deprivation

Summary Evidence that there is a critical period during which response characteristics of neurons in visual cortex of the cat may be influenced has been provided in several studies, which suggest that the period of influence is restricted to the first few months of life. Using a somewhat different experimental procedure, we have obtained evidence that cortical units retain plasticity long after the end of this period has passed. In our procedure prolonged visual deprivation was followed by exposure in a normal visual environment. The animals were maintained throughout the first year of life either in total darkness or in an enclosure illuminated intermittently by a strobe light. Following the period of deprivation, electrophysiologic recordings were taken from some of these animals. The remaining cats were permitted 6–12 months in a normally-illuminated environment prior to recording. Cats of the same age reared from birth in a normally lit environment were also recorded.Cortical neurons in cats deprived of any normal visual experience rarely show orientation selective responses. In animals allowed subsequent normal visual experience about one-half of the units studied exhibited this property. This level of response specificity is intermediate between that of normally-reared and recently-deprived animals. While most cortical units in normally-reared cats exhibit direction selectivity, this property is rarely observed in the recovery cats. A number of unit types which are rarely observed in either normal or totally deprived animals were encountered in cats that had normal exposure following prolonged deprivation. A convergent strabismus was observed, in contrast with the divergent strabismus often shown by cats immediately following prolonged visual deprivation. This shows that ocular alignment as well as cortical unit properties can remain plastic in the adult.Supported by NRC Grant No. A9939 and M.R.C. Grant No. MA5201 (to M.C.) and Grants from NIH and the Sloan Foundation (to A.H.).     

Effects of monocular deprivation on excitatory and inhibitory pathways in cat striate cortex

Summary The effects of monocular deprivation from contour vision were investigated in the striate cortex of cats. In addition to the receptive field (RF) properties of single cells responses to electrical stimulation of the deprived and the experienced optic nerve were analyzed: Evoked potentials as well as intra- and extracellularly recorded single unit responses were evaluated. The main goals were: 1. to determine to what extent the responses to electrical stimulation reflected the shift in ocular dominance apparent from the RF analysis, 2. to determine the relative effects of deprivation on excitatory and inhibitory responses and 3. to locate the site of impaired transmission in the pathway from the deprived eye. The results show that the responses to electrical stimulation reflect precisely the shift in ocular dominance apparent from the RF analysis. The evoked potentials elicited from the deprived nerve further indicate that deprivation had also affected the afferent system at the LGN level or (and) at the terminal field of the thalamo-cortical fibers. In contrast to the reduction of short latency excitatory responses to stimulation of the deprived nerve, oligosynaptic inhibition with latencies of 4–6 msec was equally well elicited by stimulation of either eye. The same was true for delayed excitatory responses which frequently occur with latencies between 40 and 80 msec after nerve stimulation. It is concluded from these results 1. that transmission between thalamic afferents and inhibitory interneurones in the cortex is less affected by deprivation than transmission in those pathways which relay cortical excitation, 2. that there is another deprivation resistant indirect pathway from the retina to the visual cortex which is probably relayed through mesencephalic structures and 3. that deprivation effects are not confined to transmission failure at the thalamo-cortical synapses but include alterations already at the presynaptic level.     

Effects of early monocular deprivation on visual input to cat nucleus of the optic tract

Single cells were recorded extracellularly in the nucleus of the optic tract (NOT) in monocularly deprived cats. Monocular deprivation had no effect on the direction specificity of these neurons, i.e. all cells in the left nucleus preferred movements from right to left and all units in the right nucleus preferred movements from left to right in the visual field. Neurons driven from the deprived eye failed to respond to stimuli moving at velocities above 10 degrees/s whereas neurons driven from the non-deprived eye responded to velocities up to and above 100 degrees/s as do neurons in normal cats. In 8 out of the 10 cats tested all cells in the two nuclei could be influenced only from the contralateral eye irrespective whether this was the deprived or the non-deprived eye. In the other two cats the influence from the non-deprived eye on cells in the ipsilateral NOT was found to be normal. This influence is mediated probably via cortico-fugal projections. In the 8 abnormal cats a clear deprivation effect could be assigned for the first time to the non-deprived eye consisting in a loss of its connections to the ipsilateral NOT. Electrical stimulation of the visual cortex revealed, however, the existence of a connection between the visual cortex and the NOT. A possible explanation for the specific deficit with visual stimulation in the cortico-pretectal synapse ipsilateral to the non-deprived eye is discussed in relation to developmental mechanisms. The conduction velocity of retinal input to the NOT and the output of the NOT to the inferior olive remained uninfluenced by visual deprivation.     

Neuronal connections of eye-dominance columns in the cat cerebral cortex after monocular deprivation

Plastic changes in intrahemisphere neuronal connections of the eye-dominance columns of cortical fields 17 and 18 were studied in monocularly deprived cats. The methodology consisted of microintophoretic administration of horseradish peroxidase into cortical columns and three-dimensional reconstruction of the areas of retrograde labeled cells. The eye dominance of columns was established, as were their coordinates in the projection of the visual field. In field 17, the horizontal connections of columns receiving inputs from the non-deprived eye via the crossed-over visual tracts were longer than the connections of the "non-crossed" columns of this eye and were longer than in normal conditions; the connections of the columns of the deprived eye were significantly reduced. Changes in the spatial organization of horizontal connections in field 17 were seen for the columns of the non-deprived eye (areas of labeled cells were rounder and the density of labeled cells in these areas were non-uniform). The longest horizontal connections in deprived cats were no longer than the lengths of these connections in cats with strabismus. It is suggested that the axon length of cells giving rise to the horizontal connections of cortical columns has a limit which is independent of visual stimulation during the critical period of development of the visual system.     

Concentration-dependent suppression by beta-adrenergic antagonists of the shift in ocular dominance following monocular deprivation in kitten visual cortex

We showed that beta-adrenergic receptor antagonists blocked the shift in ocular dominance following brief monocular deprivation in young kittens. Localized microperfusion of propranolol into the kitten visual cortex reduced the expected shift in the ocular dominance approximately 2 mm away from the center of perfusion. The blocking effect, however, did not reach an area approximately 5 mm from the perfusion center, suggesting that beta blockers work in a concentration-dependent fashion in the present paradigm. We further studied the concentration-effect relationship by widely changing the concentration of beta blockers (propranolol and sotalol) stored in an osmotic minipump. The proportion of binocular cells increased from 0.13 to 0.67 when the concentration of propranolol was increased from 10(-6)M to 10(-2)M, giving the half-maximum effect (binocularity, 0.40) at about 10(-4)M propranolol. However, the maximum binocularity obtained with the sotalol perfusion under the comparable condition was apparently much lower (0.45) than that with propranolol. Accordingly, the half-maximum binocularity (0.30) was obtained at about 10(-5)M sotalol. We also noted the presence of a linear, inverse relation between the logarithmic concentration of the beta blockers and the extent of the shift in ocular dominance as measured by the proportion of monocular cells which responded exclusively to stimulation of the nondeprived eye. The latter decreased from 0.75 to 0.25, when the former was increased from 10(-6)M to 10(-2)M (in an osmotic minipump). The two beta blockers behaved similarly in this correlation. The intracortical spread of locally perfused [3H]propranolol was studied at the end of the cortical perfusion which lasted for a week. The radioactivity was highest at the perfusion center and rapidly declined with increasing distance, leveling off approximately 3 mm from the perfusion center. The average "dilution factor" of locally perfused [3H]propranolol was calculated as about 1/170 of the original solution in an area of physiological recordings (approximately 2 mm from the perfusion center). Applying the "dilution factor" of 1/170, we estimated the approximate concentration of beta blockers needed at the recording sites to obtain the half-maximum effect; it was about 5.8 X 10(-8)M for sotalol. Taken together, the present results were interpreted as suggesting that there is a positive correlation between the number of activated beta-adrenergic receptors within the visual cortex and the extent of changes in ocular dominance following monocular deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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...     

Effects of early monocular deprivation on development of cortico-geniculate projections in the cat

Summary In 16 cats monocularly deprived from 2 to 3 weeks of age, we studied 53 striate cortical cells which were identified as projecting to the dorsal lateral geniculate nucleus (LGN) on the basis of antidromic activation from LGN and of histological localization within cortical layer VI. As in the normal cat, these cortico-geniculate cells could be classified as slow, intermediate or fast, according to their axonal conduction velocities. The sampling ratio of the slow cells (mostly unresponsive to visual stimuli) was much higher than normal. On the other hand, the ratio of the intermediate (one half were simple cells) and fast cells (all except one were complex cells) was significantly lower than the norm. Also, the average axonal conduction velocities of the complex and simple cells were significantly slower than normal. These results suggest that normal maturation of cortico-geniculate cells, particularly fast and intermediate ones, is retarded or arrested by monocular visual deprivation.Supported by a grant from the Ministry of Education of Japan     

Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation

A dramatic form of experience-dependent synaptic plasticity is revealed in visual cortex when one eye is temporarily deprived of vision during early postnatal life. Monocular deprivation (MD) alters synaptic transmission such that cortical neurons cease to respond to stimulation of the deprived eye, but how this occurs is poorly understood. Here we show in rat visual cortex that brief MD sets in motion the same molecular and functional changes as the experimental model of homosynaptic long-term depression (LTD), and that prior synaptic depression by MD occludes subsequent induction of LTD. The mechanisms of LTD, about which there is now a detailed understanding, therefore contribute to visual cortical plasticity.     

Latencies and correlation in single units and visual evoked potentials in the cat striate cortex following monocular and binocular stimulations

Summary The post-stimulus-time histograms of single unit responses recorded extracellularly from simple and complex cells in the paralyzed cat's striate cortex were compared both with the averaged visual evoked potential (VEP) recorded with the same stainless steel microelectrode and with the averaged surface VEP recorded with a silver-ball electrode applied close to the locus of microelectrode penetration. Diffuse and patterned white light stimuli, projected on a tangent screen in front of the animal, were used monocularly and binocularly at an intensity range over 2.5 log units. The latencies of spike responses to contralateral stimuli were found on the average shorter than those to ipsilateral and generally equal to those following binocular stimulation. The reciprocals of latencies as function of log stimulus intensity of the surface VEPs had the same gradient as those from averaged unit responses. In recordings from any given cell, the spike discharges displayed a fixed phase relationship to the local and another to the surface VEP, but this was not necessarily identical in different cells. These discharges may be related to the negative and positive phases of both types of slow waves. The surface and local VEPs elicited by binocular diffuse light stimulation represent the algebraic summation of the VEPs produced by ipsi- and contralateral stimulations, which confirms and expands earlier studies. No algebraic summation was found in the spike response, the sum of the two monocular responses being in most cases larger than the binocular.Supported by P.H.S. grant (project 06-810-2) from the U.S. Dept of Health, Education and Welfare, Washington, D.C.     

Effects of monocular deprivation on the expression pattern of alpha-1 and beta-1 adrenergic receptors in the kitten visual cortex

To examine how adrenergic receptors are regulated by experimental manipulation of sensory afferents, we performed immunohistochemical analysis on alpha1-, and beta1-adrenergic receptors in the brain of kittens. In normal development, these receptors were similarly expressed in both hemispheres of the occipital and frontal cortices. Notably, monocular deprivation during the sensitive period of ocular dominance plasticity significantly increased beta1-adrenergic receptor immunoreactivity in the visual cortex ipsilateral to the deprived eye. No increase in the intensity of the immunoreactivity for beta1-adrenergic receptors following monocular deprivation was found in the frontal and parietal regions of the cerebral cortex and subcortical structures, including the lateral geniculate nucleus and superior colliculus. Furthermore, such hemispheric change was not found in the alpha1-adrenergic receptor immunoreactivity following monocular deprivation. Comparisons of images, obtained by double staining for microtubule-associated protein-2 or glial fibrillary acidic protein, indicated that the increased immunoreactivity was localized on both apical dendrites of deep layer neurons and glial cells. These results indicate that the monocular deprivation during the sensitive period of ocular dominance plasticity modified beta1-adrenergic receptor immunoreactivity, including that in glial cells. Therefore, it was suggested that beta1-adrenergic receptors in the glial cells also play important roles in the regulation of ocular dominance plasticity.     

Early versus late visual cortex lesions: Effects on receptive fields in cat superior colliculus

Summary Cats that sustain lesions of the visual cortex early in life appear to perform certain visual discrimination tasks better than those operated as adults. This study sought to determine whether this recovery of visual capacities was accompanied by reorganization of single cell responses at the level of the superior colliculus. Areas 17 and 18 were ablated in adult cats and in kittens at various times during the neonatal period. Responses of units in superior colliculus ipsilateral to the lesion were recorded following a prolonged recovery period. Following cortical lesions, collicular units rarely exhibited direction selectivity, binocularity was reduced in the majority of animals, and the ocular dominance distribution was biased toward the contralateral eye. The reduction of direction selectivity and binocularity were unrelated to the animal's age at operation.This research was supported by M.R.C. Grant No. MA 5201 and NRC Grant No. A9939(to M.C.) and Grants from NIH (postdoctoral fellowshop to N.B.).     

Parvalbumin immunoreactivity: a reliable marker for the effects of monocular deprivation in the rat visual cortex.

In mammals, monocular deprivation performed during the early stages of postnatal development (critical period) dramatically affects the functional organization of the visual cortex. Since the early work of Hubel and Wiesel, the effects of monocular deprivation are accounted for by the fibers driven by the two eyes competing for the control of cortical territories. In cat and monkey striking structural changes accompany the functional effects of monocular deprivation. Also, in the rat, monocular deprivation causes functional alteration at the level of visual cortex; no structural correlates of these effects, however, have so far been described. Parvalbumin is a calcium binding protein that in the neocortex colocalizes with a subpopulation of GABAergic neurons. Here we report that in the rat monocular deprivation results in a dramatic reduction of parvalbumin-like immunoreactivity in the visual cortex contralateral to the deprived eye. This effect is due to competitive phenomena and not to visual deprivation itself, it is restricted to the binocular portion of the visual cortex and neither binocular deprivation, nor dark rearing can induce it. We conclude that parvalbumin-like immunoreactivity is a useful immunohistochemical marker for the effects of monocular deprivation in the rat visual cortex.     

The role of the lateral suprasylvian visual cortex of the cat in object-background interactions: Permanent deficits following lesions

The contribution of the lateral suprasylvian cortex to pattern recognition was studied by behavioural detection experiments in combination with bilateral lesions of different parts of the lateral suprasylvian areas (LSA) and area 7 in seven cats. In a two-alternatives forced choice task the cats had to discriminate simple outline patterns which were additively superimposed on a structured visual background made up of broadband Gaussian noise. For various stimulus conditions (moving or stationary patterns and/or background) the detection probability (P _D) of the cats was measured as a function of the signal to noise ratio (S/N). Each cat was tested before and after the lesion. Four different types of lesion could be distinguished depending on their extent: (1) lesion of parts of the (LSA); (2) lesion of parts of the LSA with undercutting of areas 17, 18 and 19; (3) lesion of area 7; (4) lesion of area 7 and parts of the LSA.

Consequences of monocular deprivation on visual behaviour in kittens

1. Kittens were raised for a period with one of their eyes closed by suture of the lids. The age at suture and the duration of deprivation were varied systematically. When the cat was a year or more old, the normal and deprived eyes were compared using behavioural procedures which made graded demands on visual function.2. In kittens deprived from birth, the duration of eye closure determined the severity of the defect in vision with the deprived eye. A cat with an eye closed for the first 4-6 weeks showed as a permanent effect only a lowering of the visual acuity. When closure was extended through the first 7 weeks the visual acuity was further lowered but the animal still showed good visual guidance of paw placement. Further extension of deprivation through the first 16 weeks led to a still more severe defect; such animals showed no indication of visual guidance of paw placement or of pattern discrimination. They were influenced visually by stimuli that differed in luminosity.3. The upper age limit of the susceptibility to deprivation was determined by varying the age at eye closure. Waiting until 1 month of age before closing the eye conferred no appreciable protection. Waiting until 2 months of age, however, reduced the damage. Deprivation starting at 4 months of age or later produced no effect we could detect. Thus, susceptibility is greatest during the second month after birth and then falls until by 4 months of age the kitten, like the adult cat, suffers no permanent consequences of monocular light and form deprivation.4. After exclusive use of the deprived eye for a period, brought about by closure of the normal eye, visual control with the deprived eye was better than in similarly deprived cats whose normal eye was never closed. Improvement in the deprived eye was also seen in an animal whose normal eye was closed after both eyes had been open for more than one year.5. Relating the behavioural results to the neurophysiological findings in the visual cortex in the same or similarly deprived cats shows that the grading of visual defects with age and length of deprivation was generally paralleled by a change in proportion of cortical cells driven by stimulation of the deprived eye. The effect of reversal of eye closure in improving behavioural control was not, however, accompanied by an increase in the ability of the deprived eye to drive cortical cells.