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Dissociating ocular dominance column development and ocular dominance plasticity: a neurotrophic model.

Recent experimental data indicate that both neurotrophic factors (NTFs) and intracortical inhibitory circuitry are implicated in the development and plasticity of ocular dominance columns. We extend a neurotrophic model of developmental synaptic plasticity, which previously failed to account correctly for the differences between monocular deprivation and binocular deprivation, and show that the inclusion of lateral cortical inhibition is indeed necessary in understanding the effects of visual deprivation in the model. In particular, we argue that monocular deprivation causes a differential shift in the balance between inhibition and excitation in cortical columns, down-regulating NTFs in deprived-eye columns and up-regulating NTFs in undeprived-eye columns; during binocular deprivation, however, no such shift occurs. We thus postulate that the response to visual deprivation is at the level of the cortical circuit, while the mechanisms of afferent segregation are at the molecular or cellular level. Such a dissociation is supported by recent experimental work challenging the assumption that columnar organisation develops in an activity-dependent, competitive fashion. Our extended model also questions recent attempts to distinguish between heterosynaptic and homosynaptic models of synaptic plasticity.

Animals↗

Ocular prevalence versus ocular dominance.

UNLABELLED: Ocular dominance manifests itself in tests that contain stereo-objects with a disparity beyond Panum's area, e.g. in pointing a finger. These tests force subjects to decide in favour of one or the other eye. In contrast, ocular prevalence is determined using stereo-targets imaged within Panum's areas. These tests allow a graded quantification of the balance between the eyes. Here we present the computer-based Freiburg Ocular Prevalence Test in which stereo-disparate targets have to be aligned, and compare it with the Haase Stereo-balance Test that requires an estimation of the horizontal distance between stationary stereo-disparate objects. In addition, we compare ocular prevalence with ocular dominance. METHODS: (1) We measured the influence of a neutral-grey filter in front of one eye to assess the suitability of the Freiburg and the Haase Tests in revealing graded amounts of ocular prevalence. (2) About 20 subjects with equal vision of their two eyes underwent the Freiburg and the Haase Tests for ocular prevalence, and Parson's Monoptoscope Test for ocular dominance. RESULTS: (1) In both the Freiburg and the Haase Tests, the neutral-grey filter shifted ocular prevalence by about 50%. (2) An ocular prevalence of more than 10% occurred in 13 of the 20 subjects using the Freiburg, and in 14 using the Haase Test. On average, the ocular prevalence was 24.1+/-3.8% in the Freiburg and 32.0+/-8.2% in the Haase Test. The dominant eye coincided with the prevalent eye in 15 of the 20 subjects. DISCUSSION: The effect of the neutral-grey filter indicated that both the Freiburg and the Haase Tests can be used to measure fractions of ocular prevalence, although the Freiburg Test carries a higher reproducibility. Spontaneous ocular prevalence occurs frequently in persons with equal vision of their two eyes. This suggests that ocular prevalence does not represent a condition that requires treatment. Rather, partial suppression of one eye, the correlate of ocular prevalence, may play a physiological role in that it helps to disregard double images at stereo-disparities close to the limits of Panum's area.

Adult↗

How can squint change the spacing of ocular dominance columns?

The pattern of ocular dominance columns in primary visual cortex of mammals such as cats and macaque monkeys arises during development by the activity-dependent refinement of thalamocortical connections. Manipulating visual experience in kittens by the induction of squint leads to the emergence of ocular dominance columns with a larger size and larger column-to-column spacing than in normally raised animals. The mechanism underlying this phenomenon is presently unknown. Theory suggests that experience cannot influence the spacing of columns if the development proceeds through purely Hebbian mechanisms. Here we study a developmental model in which Hebbian mechanisms are complemented by activity-dependent regulation of the total strength of afferent synapses converging onto a cortical neurone. We show that this model implies an influence of visual experience on the spacing of ocular dominance columns and provides a conceptually simple explanation for the emergence of larger sized columns in squinting animals. Assuming that during development cortical neurones become active in local groups, which we call co-activated cortical domains (CCDs), ocular dominance segregation is controlled by the size of these groups: (1) Size and spacing of ocular dominance columns are proportional to the size sigma of CCDs. (2) There is a critical size sigma* of CCDs such that ocular dominance columns form if sigma sigma*. This critical size of CCDs is determined by the correlation functions of activity patterns in the two eyes and specifies the influence of experience on ocular dominance segregation. We show that sigma* is larger with squint than with normal visual experience. Since experimental evidence indicates that the size of CCDs decreases during development, ocular dominance columns are predicted to form earlier and with a larger spacing in squinters compared to normal animals.

Animals↗

Subplate neuron ablation alters neurotrophin expression and ocular dominance column formation.

Ocular dominance column formation in visual cortex depends on both the presence of subplate neurons and the endogenous expression of neurotrophins. Here we show that deletion of subplate neurons, which supply glutamatergic inputs to visual cortex, leads to a paradoxical increase in brain-derived neurotrophic factor mRNA in the same region of visual cortex in which ocular dominance columns are absent. Subplate neuron ablation also increases glutamic acid decarboxylase-67 levels, indicating an alteration in cortical inhibition. These observations imply a role for this special class of neurons in modulating activity-dependent competition by regulating levels of neurotrophins and excitability within a developing cortical circuit.

Base Sequence↗

Ocular dominance and amblyopia.

Ocular dominance, as measured in sighting tests, involves a temporary suppression of the input from the non-dominant eye in order to avoid diplopia. Amblyopia ex anopsia may be viewed as a long term suppression of the input from one eye for the same reason. In the absence of anisometropia, paralysis of extra ocular muscles, or other factors which would tend to determine which eye would manifest suppression, the non-dominant sighting eye should be more likely to develop amblyopia given the presence of strabismus. A sample of 258 amblyopes supports this prediction based on the population norms for sighting dominance.

Amblyopia↗

Lifelong learning: ocular dominance plasticity in mouse visual cortex.

Ocular dominance plasticity has long served as a successful model for examining how cortical circuits are shaped by experience. In this paradigm, altered retinal activity caused by unilateral eye-lid closure leads to dramatic shifts in the binocular response properties of neurons in the visual cortex. Much of the recent progress in identifying the cellular and molecular mechanisms underlying ocular dominance plasticity has been achieved by using the mouse as a model system. In this species, monocular deprivation initiated in adulthood also causes robust ocular dominance shifts. Research on ocular dominance plasticity in the mouse is starting to provide insight into which factors mediate and influence cortical plasticity in juvenile and adult animals.

Animals↗

Unstable ocular dominance and reading ability.

An ocular anomaly, unstable ocular dominance, has been shown to be associated with poor reading performance in clinically selected subjects. A study is reported in which this anomaly was examined in a nonclinical sample. Two groups of children of similar reading performance and IQ but differing in chronological age were selected. The older children had a mean discrepancy between their reading and chronological age of 19 months. Unstable ocular dominance was more frequent in these poor readers. The hypothesis that this instability would lead to more errors and longer decision times for distinguishing left-right mirror-image figures was not supported. If unstable ocular dominance is to be established as anything other than a correlate of specific reading retardation, it is necessary to establish the processes through which it is operative. These have yet to be determined.

Child↗

Development of cortical circuits: lessons from ocular dominance columns.

The development of ocular dominance columns has served as a Rosetta stone for understanding the mechanisms that guide the construction of cortical circuits. Traditionally, the emergence of ocular dominance columns was thought to be closely tied to the critical period, during which columnar architecture is highly susceptible to alterations in visual input. However, recent findings in cats, monkeys and ferrets indicate that columns develop far earlier, more rapidly and with considerably greater precision than was previously suspected. These observations indicate that the initial establishment of cortical functional architecture, and its subsequent plasticity during the critical period, are distinct developmental phases that might reflect distinct mechanisms.

Animals↗

Binocular impulse blockade prevents the formation of ocular dominance columns in cat visual cortex.

Ocular dominance columns in the cat's visual cortex appear to develop out of an initially overlapping projection by a progressive segregation of the geniculocortical afferents serving the 2 eyes (reviewed in LeVay and Stryker, 1979). To determine whether electrical activity in the visual afferent pathway is involved in this normal, developmental rearrangement of synaptic connections, we blocked the discharge of retinal ganglion cells in both eyes by making repeated intravitreal injections of tetrodotoxin (TTX) during the period in which geniculocortical afferent segregation would normally be taking place. Control experiments for the side effects of the injection procedure, the systemic effects of TTX, and the effects of visual deprivation were carried out, and a series of normal animals of appropriate ages was also studied. We then examined the effects of retinal blockade and the various control procedures on the formation of ocular dominance columns using an anatomical assay, the autoradiographic labeling of geniculocortical afferent terminals in layer IV of the visual cortex by the transneuronal transport of tritiated proline injected into 1 eye, and a physiological assay, the ocular dominance of single cortical cells recorded extracellularly. After retinal TTX blockade, layer IV was labeled uniformly without periodic fluctuation in grain density, and nearly all cortical cells were driven well through both eyes. These assays thus indicated that retinal blockade completely blocked the formation of ocular dominance columns, unlike any of the control procedures, suggesting that the spontaneous maintained discharge of retinal ganglion cells may have an important role in the normal development of binocular connections in the visual cortex.

Animals↗

Ocular dominance and disparity coding in cat visual cortex.

The orientation selectivity, ocular dominance, and binocular disparity tuning of 272 cells in areas 17 and 18 of barbiturate-anesthetized, paralyzed cats were studied with automated, quantitative techniques. Disparity was varied along the axis orthogonal to each cell's best orientation. Binocular correspondence was established by means of a reference electrode positioned at the boundary of lamina A and A1 in the area centralis representation of the lateral geniculate nucleus. Measures were derived that expressed each cell's disparity sensitivity and best disparity and the shape and slope of its tuning curve. Cells were found that corresponded to categories described by previous authors ("disparity-insensitive," "tuned excitatory," "near," and "far" cells), but many others had intermediate response patterns, or patterns that were difficult to categorize. Quantitative analysis suggested that the various types belong to a continuum. No relationship could be established between a cell's best orientation and its ocular dominance or any aspect of its disparity tuning. There was no relationship between a cell's ocular dominance and its sensitivity to disparity. Ocular dominance and best disparity were related. As reported by others, cells with best disparities close to zero (the fixation plane) tended to have balanced ocularity, while cells with best disparities in the near or far range had a broad distribution of ocular dominance. Among cells with receptive fields near the vertical meridian, those preferring far disparities tended to be dominated by the contralateral eye, and those preferring near disparities by the ipsilateral eye. It is suggested that this relationship follows from the geometry of near and far images and the pattern of decussation in the visual pathway. There was a significant grouping of cells with similar best disparities along tangential electrode tracks. We believe that this grouping is due to the columnar organization for ocular dominance and the relationship between ocular dominance and best disparity. No evidence was found for a columnar segregation of disparity-sensitive and disparity-insensitive cells.

Animals↗

Quantitative measurement of ocular dominance using binocular rivalry induced by retinometers.

PURPOSE: To develop a new method using binocular rivalry and retinometers to quantitatively examine ocular dominance and to investigate the magnitude of ocular dominance in cataract patients preoperatively and postoperatively. SETTING: Eye Clinic, Kitasato University School of Medicine Hospital, Sagamihara, Kanagawa, Japan. METHODS: The duration of exclusive visibility of the dominant and nondominant eye target in binocular rivalry were measured in 60 healthy volunteers (study 1) and preoperatively and postoperatively in 10 cataract patients (study 2). Rivalry targets were presented directly to the retina of each eye using 2 retinometers. Subjects reported the exclusive visibility of 1 eye target, and the total duration of exclusive visibility for each eye in dominant and nondominant eye trials was evaluated. RESULTS: In study 1, the magnitude of ocular dominance was quantitatively assessed with 4 grades based on differences in total duration of exclusive visibility between dominant and nondominant eyes. In study 2, magnitude of ocular dominance could be evaluated in all cataract patients regardless of refractive and cataract conditions. Magnitude of ocular dominance displayed significant correlations between preoperative and postoperative conditions (simple regression, P<.001). CONCLUSIONS: Ocular dominance can be quantitatively evaluated using this new method based on binocular rivalry and retinometers, particularly in cataract patients. Magnitude of ocular dominance may indicate preoperatively whether a patient with cataracts will have sufficient ocular dominance to adjust to monovision correction.

Adult↗

Ocular dominance columns in New World monkeys.

Squirrel monkeys normally lack ocular dominance columns in V1. This study shows that squirrel monkeys can exhibit clear ocular dominance columns if they are made strabismic within a few weeks of birth. Columns were seen only in layer 4C beta and were coarser than the overlying blob pattern in the same animal. In physiological recordings from layer 4C of a normal squirrel monkey, single units were mostly monocular, but units driven by the two eyes were intermixed. These results suggest that in squirrel monkeys activity-dependent mechanisms do normally segregate geniculate inputs from the two eyes, but on a much finer scale than in Old World primates. Strabismic owl monkeys also showed ocular dominance columns; normal owl monkeys showed variable expression. Because ocular dominance columns, when present in New World monkeys, tend to occur in later-maturing parts of layer 4C, I hypothesize that a difference in the relative timing of the maturation of geniculocortical inputs and intracortical lateral connectivity explains the variability of ocular dominance column expression in New World monkeys.

Animals↗

Ocular dominance plasticity in mature mice.

Ocular dominance plasticity, classically thought to be restricted to an early critical period, is now described by Sawtell et al. in fully adult mice. Adult plasticity, like critical period plasticity, requires cortical NMDA receptors but involves different functional changes in cortical circuits.

Animals↗

Geometry of orientation and ocular dominance columns in monkey striate cortex.

In addition to showing that ocular dominance is organized in slabs and that orientation preferences are organized in linear sequences likely to reflect slabs, Hubel and Wiesel (1974a) discussed the intriguing possibility that slabs of orientation might intersect slabs of ocular dominance at some consistent angle. Advances in optical imaging now make it possible to test this possibility directly. When maps of orientation are analyzed quantitatively, they appear to arise from a combination of at least two competing themes: one where orientation preferences change linearly along straight axes, remaining constant along perpendicular axes and forming iso-orientation slabs along the way, and one where orientation preferences change continuously along circular axes, remaining constant along radial axes and forming singularities at the centers of the spaces enclosed. When orientation patterns are compared with ocular dominance patterns from the same cortical regions, quantitative measures reveal (1) that singularities tend to lie at the centers of ocular dominance columns, (2) that linear zones (arising where orientation preferences change along straight axes) tend to lie at the edges of ocular dominance columns, and (3) that the short iso-orientation bands within each linear zone tend to intersect the borders of ocular dominance slabs at angles of approximately 90 degrees.

Animals↗

The overall pattern of ocular dominance bands in cat visual cortex.

This study describes the overall arrangement of geniculocortical input representing the system of cortical ocular dominance bands in layer IV of striate cortex in the adult cat. The pattern of ocular dominance bands was revealed by transneuronal transport of the intraocularly injected tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Our data indicate that this procedure does not damage the retina and that it results in relatively uniform uptake and transport of the tracer. Using previously published techniques (Olavarria and Van Sluyters, 1983, 1985), both cortical hemispheres of each cat were unfolded, flattened and tangentially sectioned. Analysis of the WGA-HRP labeling patterns in these sections revealed a relatively continuous network of irregularly branching bands in layer IV of area 17 in both hemispheres. Because of a systematic difference in the level of interband labeling, ocular dominance bands appear less distinct in the hemisphere contralateral to the injected eye. There is also a tendency for interband labeling to be greater in cortical regions that represent the more peripheral aspects of the binocular portion of the visual field. The width of an individual ocular dominance band in the cat fluctuates, so that it appears to be made up of a series of uniformly sized, roughly circular beads of label. The diameter of these beads averages 667 micron, and preliminary counts indicate that there are 650-675 beads in each striate cortex. Contrary to earlier suggestions, in 4 out of 6 hemispheres analyzed quantitatively there was no tendency for ocular dominance bands to be oriented along a preferred axis in cat striate cortex, including an axis orthogonal to the border between areas 17 and 18. Ocular dominance bands in area 18 appear to be broader than those in area 17, and they seem to have a greater tendency to be oriented orthogonal to the 17/18 border than those in area 17. Compared with the ocular dominance pattern in monkey striate cortex, the ocular dominance pattern in the cat is much less regular. In general, cat ocular dominance bands appear to fluctuate more in width, to change direction more often, and to be less likely to run orthogonal to the 17/18 border. The greater regularity of the primate ocular dominance pattern may be related to differences in the way in which the visual hemifield is mapped onto the striate cortex in these 2 species.

Animals↗

Amblyopia induced by anisometropia without shrinkage of ocular dominance columns in human striate cortex.

Amblyopia can be induced by opacity of the ocular media (e.g., cataract), misalignment of the ocular axes (strabismus), or unequal refractive error in the eyes (anisometropia). Experiments in monkeys have shown that early monocular eyelid suture, a model of amblyopia caused by cataract, results in shrinkage of the eye's ocular dominance columns in striate cortex. This reduction of the geniculocortical projection from the deprived eye has been thought to explain in part the mechanism of amblyopia. We labeled the ocular dominance columns in monkeys with amblyopia by using cytochrome oxidase histochemistry. In animals rendered amblyopic by early unilateral eyelid suture, no pattern of cytochrome oxidase activity appeared in layer IVc. Outside layer IVc, alternating rows of light and dark patches were present; the pale patches fit in register with the shrunken ocular dominance columns of the deprived eye, which were labeled by autoradiography. Subsequent removal of one eye caused a striking cytochrome oxidase pattern to emerge in layer IVc that correlated precisely with the shrunken (deprived eye) and expanded (normal eye) ocular dominance columns. This correlation was shown by injecting one eye with [3H]proline. It has remained unsettled whether other forms of amblyopia are accompanied by shrinkage of ocular dominance columns. To address this issue, in an analogous clinical case, we examined the pattern of cytochrome oxidase activity in a human subject with a history of anisometropic amblyopia who suffered a lesion of one optic nerve shortly before death. The ocular dominance columns were normal in width, indicating that some forms of amblyopia occur without shrinkage of ocular dominance columns.

Amblyopia↗

Binocular sighting ocular dominance changes with different angles of horizontal gaze.

BACKGROUND AND PURPOSE: Ocular dominance testing is generally carried out in the primary position. A change of eye dominance when viewing in the contralateral field of horizontal gaze has recently been reported. The purpose of this study was to determine whether this occurs with other tests of eye dominance. METHODS: Ten right handed females (mean age 21.6 +/-0.8 years) with normal binocular single vision and right eye ocular dominance in primary position were tested for ocular dominance on three tests (pointing, hole-in-card, Miles ABC) performed fixing at positions at 10 degree intervals from 40 degrees left gaze to 40 degrees right gaze, with the head stationary. Four trials were undertaken in each position for each test. RESULTS: Not all participants showed a change in dominance in left gaze on all of the tests. However, a change did occur at a median of 30 degrees for the hole- in-card and Miles ABC tests and 20 degrees for the pointing test. Examining the position of change across the 3 tests, a borderline "statistically significant" difference occurred (p=0.055, Friedman test). A "statistically significant" difference was shown between the hole-in-card and pointing tests (p=0.041, Wilcoxon signed ranks test). For pointing versus Miles ABC, p=0.084; and hole-in-card versus Miles ABC, p=0.705. CONCLUSIONS: A change in eye dominance occurs when viewing in the contralateral field. Differences may exist in the angle at which this occurs due to the different conditions of the various tests for ocular dominance.

Adult↗

Reemergence of ocular dominance plasticity during recovery from the effects of propranolol infused in kitten visual cortex.

We wanted to know whether ocular dominance plasticity can increase under the condition in which the number of available beta adrenoreceptors is expected to increase within kitten visual cortex. We adopted a paradigm in which monocular lid suture was carried out some time after the termination of direct infusion of the cortex with a beta adrenoreceptor antagonist. A significant change in ocular dominance was obtained as shown by a decrease in binocular cortical neurons, when time interval between the end of the d,l-propranolol infusion and the start of monocular deprivation was one week. With a 3-week interval (the longest tested), an even greater change in ocular dominance was evident. This consisted of a marked decrease in binocular neurons and a shift in ocular dominance toward the nondeprived eye. In a control study an inert stereoisomer, d-propranolol, did not block the ocular dominance shift. These results were interpreted as suggesting that the level of ocular dominance plasticity becomes high in parallel to an expected increase in availability of beta adrenoceptors for endogenous noradrenaline (NA). We next asked whether it is possible to accelerate or decelerate the naturally occurring recovery of ocular dominance plasticity. When either NA or tunicamycin (an inhibitor of protein glycosylation) was infused into the same cortical area immediately after the end of the propranolol infusion, opposite effects were observed: exogenous NA accelerated the recovery of the shift in ocular dominance and tunicamycin suppressed it. When tunicamycin infusion was delayed by one week, however, its suppressive effect was negligible. Thus, the restoration of ocular dominance plasticity seems to occur in parallel to an increase in the availability of beta adrenoreceptors for endogenous as well as exogenous NA.

Animals↗