The ocular dominance and receptive field properties of visual cortex cells of cats following long-term transection of the optic chiasm and monocular deprivation during adulthood

Plasticity-induced interhemispheric transfer of visual information to cortical cells was studied in adult cats. The direct contralateral visual pathway was surgically eliminated permitting binocularity only by callosal transfer. In order to enhance the interhemispheric transfer, one hemisphere was made less visually active by depriving it chronically from visual input. Single cell recording was made in areas 17-18 boundary, the callosal projection zone, of operated (OC), operated and deprived (OCMD), and normal control cats. In the OCMD cats, greater than 90% of the cells in each hemisphere reacted ipsilaterally to the deprived or non-deprived eye. Only 3.1% of the cells in both hemispheres of the OCMD cats and 3.9% in the OC cats had contralateral input via the corpus callosum. The two hemispheres were similar in the selectivity of their cells to stimulus orientation and direction. The average receptive field area of the OCMD cats was also similar for the ipsilaterally driven cells in the two hemispheres; it was 1.2 degrees 2 for the deprived eye and 1.1 degrees 2 for the normal eye. The receptive fields (greater than 95%) of both eyes of the OCMD cats were found in the nasal visual hemifields and greater than 70% of them were at eccentricities of less than 5 degrees from the vertical meridian. The disappearance of the temporal (contralateral) hemifields in these cats and the physiological properties of their cortical cells were determined merely by the chiasm transection which had thus induced nearly complete interhemispheric separation. No effect of the monocular deprivation, in normal adult cats or in cats with chiasm transection was found, even after long periods (greater than 7 months). Therefore, plasticity-induced interhemispheric transfer of visual information was not found during adulthood.     

Functional plasticity in extrastriate visual cortex following neonatal visual cortex damage and monocular enucleation

Neonatal lesions of primary visual cortex (areas 17, 18 and 19; VC) in cats lead to significant changes in the organization of visual pathways, including severe retrograde degeneration of retinal ganglion cells of the X/beta class. Cells in posteromedial lateral suprasylvian (PMLS) cortex display plasticity in that they develop normal receptive-field properties despite these changes, but they do not acquire the response properties of striate neurons that were damaged (e.g., high spatial-frequency tuning, low contrast threshold). One possibility is that the loss of X-pathway information, which is thought to underlie striate cortical properties in normal animals, precludes the acquisition of these responses by cells in remaining brain areas following neonatal VC damage. Previously, we have shown that monocular enucleation at the time of VC lesion prevents the X-/beta-cell loss in the remaining eye. The purpose of the present study was to determine whether this sparing of retinal X-cells leads to the development of striate-like response properties in PMLS cortex. We recorded the responses of PMLS neurons to visual stimuli to assess spatial-frequency tuning, spatial resolution, and contrast threshold. Results indicated that some PMLS cells in animals with a neonatal VC lesion and monocular enucleation displayed a preference for higher spatial frequencies, had higher spatial resolution, and had lower contrast thresholds than PMLS cells in cats with VC lesion alone. Taken together, these results suggest that preserving X-pathway input during this critical period leads to the addition of some X-like properties to PMLS visual responses.     

Midsagittal transection of the optic chiasm and the corpus callosum induces visual split brain in cats: the effect on ocular dominance and responsiveness to cells in the visual cortex

The geniculocortical pathways from the contralateral eye and the callosal pathway were interrupted in cats in order to study how cortical cells are influenced by changes induced in the interhemispheric transfer of visual information. Unit recording was carried out from areas 17 and 18 boundary, the callosal projection zone. The ocular dominance distribution of cortical cells showed absence of interhemispheric interaction. The visual areas in the two sides of the brain thus functioned independently, presenting a condition of visual split brain. This also has been reflected by the absence of compensatory visual inputs via an alternative commissural pathway. Furthermore, remarkable diminution in the excitability level was found as indicated by the reduction in the proportion of visually responsive cells. Finally, the results of the split brain cat reflect the condition of the individual operations from which it is composed.     

Lack of binocularity in cells of area 19 of cat visual cortex following monocular deprivation

We have studied the visual receptive field properties of neurons in cortical area 19 of monocularly deprived cats. Almost all visually responsive units responded to stimulation of the non-deprived eye only. Receptive field properties assessed through the non-deprived eye were found to be normal. Monocular deprivation appears thus to have sharply reduced the normal binocularity of neurons in area 19. Since the W-cell component of the visual pathways provide the predominant input to area 19, our results suggest that W-cells are vulnerable to environmental manipulation.     

Susceptibility to monocular deprivation following immersion in darkness either late into or beyond the critical period

An extended duration of darkness starting near the time of birth preserves immature neuronal characteristics and prolongs the accentuated plasticity observed in young animals. Brief periods of complete darkness have emerged as an effective means of restoring a high capacity for neural plasticity and of promoting recovery from the effects of monocular deprivation (MD). We examined whether 10 days of darkness imposed in adulthood or beyond the peak of the critical period could rejuvenate the ability of MD to reduce the size of neuron somata within deprived layers of the cat dorsal lateral geniculate nucleus (dLGN). For adult cats subjected to 10 days of darkness before 7 days of MD, we observed no alteration in neuron size or neurofilament labeling within the dLGN. At 12 weeks of age, MD that followed immediately after 10 days of darkness produced an enhanced reduction of neuron soma size within deprived dLGN layers. For this age we observed that 10 days of darkness also enhanced the loss of neurofilament protein within deprived dLGN layers. These results indicate that, although 10 days of darkness in adulthood does not enhance the susceptibility to 7 days of MD, darkness imposed near the trailing edge of the critical period can restore a heightened susceptibility to MD more typical of an earlier developmental stage. The loss of neurofilament in juveniles exposed to darkness prior to MD suggests that the enhanced capacity for structural plasticity is partially rooted in the ability of darkness to modulate molecules that inhibit plasticity. J. Comp. Neurol. 524:2643–2653, 2016. © 2016 Wiley Periodicals, Inc.     

Prolonged sensitivity to monocular deprivation in dark-reared cats: effects of age and visual exposure

Previous studies have shown that the response properties of cortical cells of cats reared in darkness throughout the naturally-occurring critical period can still be modified by environmental manipulation. Here the effects of extremely prolonged dark-rearing, and of light exposure before or after dark-rearing on subsequent susceptibility to monocular deprivation are examined. Monocular deprivation remains effective in altering cortical ocular dominance even in cats which have been dark-reared for up to 2 years, long after the end of the naturally occurring critical period. The effects of monocular deprivation are, however, less pronounced in these cats than in animals dark-reared for shorter periods of time. The effects of visual exposure before dark-rearing were examined by allowing kittens 2 months of normal vision followed by 3 months of dark-rearing. Then, the effects of monocular suture were compared among these kittens and: (1) 2-month-old normal kittens (which had the same amount of visual exposure as the experimental animals); and (2) 5-month-old normal kittens (of the same age as the experimental animals). The results show that monocular deprivation is more effective in the experimental animals than in normal kittens of the same age, but less effective than in normal 2-month-old animals. The effects of visual exposure after dark-rearing were examined by allowing animals dark-reared for 4 months varied durations of binocular visual exposure before monocular suture. Susceptibility to monocular suture disappears about 6 weeks after the dark-reared animals are brought into the light.     

Down-regulation of β-adrenergic receptor following long-term monocular deprivation in cat visual cortex

To examine how adrenergic receptor binding is modified by experimental manipulation of sensory afferent, we carried out binding experiments (membrane fraction and in vitro autoradiography) for both ₂- and β-adrenergic receptors in the brain of cats which had been deprived of vision in one eye. In the cerebral cortex of control animals, β-adrenergic receptor (β-AR) binding was found to be higher in the occipital regions than in other regions, while ₂-AR binding was relatively uniform. Monocular deprivation throughout the postnatal sensitive period (1–7 month of age) significantly decreased β-AR binding in the visual cortex and lateral geniculate nucleus. Scatchard plot analysis in the visual cortex showed ca. 50% reduction in B_max and little change in K_d No significant difference was found in ₂-AR binding following monocular deprivation. Similar extent of down-regulation in β-AR binding was confirmed in all layers of visual cortex using autoradiography.     

Initial hypertrophy of cells in undeprived laminar of the lateral geniculate nucleus of the monkey following early monocular visual deprivation

Comparisons of mean cell area in the lateral geniculate nucleus between normal and monocularly deprived Rhesus monkeys show that closure started in the first few days of life produces an initial hypertrophy of up to 25% affecting undeprived parvocellular cells. Hypertrophy is maximal at 4 weeks. Following this there is a later shrinkage affecting both deprived and undeprived parvocellular cells so that ultimately undeprived parvocellular cells are about 10% smaller and deprived parvocellular cells about 35% smaller than corresponding cells in normal animals.     

Critical period for the marked loss of retinal X-cells following visual cortex damage in cats

Visual cortex damage in newborn kittens produces a 78% loss of retinal X-cells whereas damage in adult cats produces only a 22% loss. Retinal Y- and W-cells are unaffected. The present experiment showed that the critical period for the severe loss of retinal X-cells ends between birth and 2 weeks of age. These results have implications for understanding the neural mechanisms of recovery from early visual cortex damage.     

A switch from inter‐ocular to inter‐hemispheric suppression following monocular deprivation in the rat visual cortex

Binocularity is a key property of primary visual cortex (V1) neurons that is widely used to study synaptic integration in the brain and plastic mechanisms following an altered visual experience. However, it is not clear how the inputs from the two eyes converge onto binocular neurons, and how their interaction is modified by an unbalanced visual drive. Here, using visual evoked potentials recorded in the juvenile rat V1, we report evidence for a suppressive mechanism by which contralateral eye activity inhibits responses from the ipsilateral eye. Accordingly, we found a lack of additivity of the responses evoked independently by the two eyes in the V1, and acute silencing of the contralateral eye resulted in the enhancement of ipsilateral eye responses in cortical neurons. We reverted the relative cortical strength of the two eyes by suturing the contralateral eye shut [monocular deprivation (MD)]. After 7 days of MD, there was a loss of interocular suppression mediated by the contralateral, deprived eye, and weak inputs from the closed eye were functionally inhibited by interhemispheric callosal pathways. We conclude that interocular suppressive mechanisms play a crucial role in shaping normal binocularity in visual cortical neurons, and a switch from interocular to interhemispheric suppression represents a key step in the ocular dominance changes induced by MD. These data have important implications for a deeper understanding of the key mechanisms that underlie activity‐dependent rearrangements of cortical circuits following alteration of sensory experience.     

Layer- and cell-type-specific subthreshold and suprathreshold effects of long-term monocular deprivation in rat visual cortex

Connectivity and dendritic properties are determinants of plasticity that are layer and cell-type specific in the neocortex. However, the impact of experience-dependent plasticity at the level of synaptic inputs and spike outputs remains unclear along vertical cortical microcircuits. Here I compared subthreshold and suprathreshold sensitivity to prolonged monocular deprivation (MD) in rat binocular visual cortex in layer 4 and layer 2/3 pyramids (4Ps and 2/3Ps) and in thick-tufted and nontufted layer 5 pyramids (5TPs and 5NPs), which innervate different extracortical targets. In normal rats, 5TPs and 2/3Ps are the most binocular in terms of synaptic inputs, and 5NPs are the least. Spike responses of all 5TPs were highly binocular, whereas those of 2/3Ps were dominated by either the contralateral or ipsilateral eye. MD dramatically shifted the ocular preference of 2/3Ps and 4Ps, mostly by depressing deprived-eye inputs. Plasticity was profoundly different in layer 5. The subthreshold ocular preference shift was sevenfold smaller in 5TPs because of smaller depression of deprived inputs combined with a generalized loss of responsiveness, and was undetectable in 5NPs. Despite their modest ocular dominance change, spike responses of 5TPs consistently lost their typically high binocularity during MD. The comparison of MD effects on 2/3Ps and 5TPs, the main affected output cells of vertical microcircuits, indicated that subthreshold plasticity is not uniquely determined by the initial degree of input binocularity. The data raise the question of whether 5TPs are driven solely by 2/3Ps during MD. The different suprathreshold plasticity of the two cell populations could underlie distinct functional deficits in amblyopia.     

Distribution of visual callosal projection neurons in hamsters subjected to transection of the optic radiations on the day of birth

The optic radiations of hamsters were transected on the day of birth and visual callosal projections in these animals were traced using retrograde transport of either horseradish peroxidase (HRP) or the fluorescent tracers True blue (TB) or Diamidino yellow (DY) when the animals reached maturity (greater than 45 days of age). In the hemisphere ipsilateral to the neonatal lesion, the distribution of callosal cells was markedly altered. These neurons were almost completely restricted to a continuous band in lower lamina V and the upper portion of layer VI. Anterograde HRP transport to the deafferented hemisphere also revealed an abnormal distribution of callosal terminals. The band of labelling that is located along the 17-18a border in the normals was much broader than is normally the case. In the hemisphere contralateral to the lesion, the distributions of callosal cells and terminals were essentially normal. Labelled neurons were located in the infragranular layers (primarily lower layer V and the upper part of lamina VI) throughout area 17 and also in layers II-IV in the 17-18a border region. Anterograde labelling was visible in layers V and VI throughout the mediolateral extent of the dorsal posterior neocortex and supragranular labelling was restricted to the lateral portion of area 17 and medial 18a. These results suggest that the normal thalamic projection to the visual cortex is necessary for the establishment of the strip of supragranular callosal projection neurons which is normally located in the 17-18a border region, but not for the establishment (or maintenance) of callosal projections by large numbers of neurons in the infragranular laminae. They show further that neonatal transection of the optic radiations results in reduction in the correspondence between the distributions of callosal cells and terminals in the deafferented hemisphere.     

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.     

Evidence for degeneration of retinal W cells following early visual cortical removal in cats

Size and distribution of ganglion cells surviving unilateral visual cortical removal at 5-7 days of age were examined in domestic cats. Such lesions were expected to result in a substantial loss of X cells in ipsilateral temporal and contralateral nasal retina, leaving ipsilateral nasal and contralateral temporal retina to serve as intact controls. A computer model of normal retinal ganglion cell topography was used to make qualitative predictions of the distribution of surviving ganglion cells. Contrary to expectations, a visual streak was no more prominent in the distribution of surviving cells than in the distribution of the normal ganglion cell population. The magnitude of ganglion cell loss, furthermore, was at least twice as great in nasal retina as in temporal retina. In nasal retina, the cell loss extended well into the small-medium size range, while in temporal retina, cell loss was restricted to the large-medium size range. Taken together, the differential magnitude of cell loss in nasal and temporal retina and the greater loss of small-medium cells in nasal retina cannot be explained by the exclusive degeneration of X cells and suggest that many of the degenerated ganglion cells were medium-sized W or gamma cells. These cells, therefore, share the susceptibility of retinal X cells to early cortical ablation. Surviving gamma cells in both nasal and temporal retina appeared to increase in soma size which may explain why their decreased numbers were not detected in previous physiological studies. Alpha cells, at least in nasal retina, decreased in some size.     

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 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.     

Repeated measurements of contrast sensitivity reveal limits to visual plasticity after early binocular deprivation in humans

Contrast sensitivity improves in visually normal children until 7 years of age and is impaired in children who experienced early visual deprivation from bilateral congenital cataracts. Here, we investigated whether the deficits after early visual deprivation change during childhood by retesting the contrast sensitivity of seven patients treated for bilateral congenital cataract who had been first tested before 7.5 years of age, and of two patients first tested after 11 years of age. For the younger group, contrast sensitivity at low spatial frequencies improved after 1- and 2-year intervals, while their sensitivity at mid and high spatial frequencies did not change. There was no systematic change in the two older patients. The results indicate that early visual input sets up the neural substrate for later improvement in contrast sensitivity at mid and high spatial frequencies. However, there is sufficient plasticity during middle childhood to allow some recovery at low spatial frequencies. The results shed new light on the role of early visual experience and the nature of developmental plasticity.