Ocular Dominance Columns Research Articles

Decorrelation of Cerebral Visual Inputs as the Sufficient Cause of Infantile Esotropia

Background and PurposeHuman infants at greatest risk for esotropia are those who suffer cerebral insults that could decorrelate signals from the two eyes during an early critical period of binocular, visuomotor development. The authors reared normal infant monkeys under conditions of binocular decorrelation to determine if this alone was sufficient to cause esotropia, and associated behavioral as well as neuroanatomic deficits.MethodsBinocular decorrelation was imposed using prism-goggles for durations of 3–24 weeks (control monkeys wore piano goggles), emulating unrepaired strabismus of durations 3 months to 2 years in human infants. Behavioral recordings were obtained, followed by neuroanatomic analysis of ocular dominance columns and binocular, horizontal connections in the striate visual cortex (area V1).ResultsConcomitant, constant esotropia developed in each monkey exposed to decorrelation for a duration of 6–24 weeks. The severity of ocular motor signs (esotropia angle; dissociated vertical deviation; latent nystagmus; pursuit/optokinetic tracking asymmetry; fusional vergence deficits), and the loss of V1 binocular connections increased as a function of decorrelation duration. Stereopsis was deficient and motion visually evoked potentials were asymmetric. Monkeys exposed to decorrelation for 3 weeks showed transient esotropia, but regained normal alignment, visuomotor behaviors, and binocular V1 connections.ConclusionsBinocular decorrelation is a sufficient cause of infantile esotropia when imposed during a critical period of visuomotor development. The systematic relationship between severity of visuomotor signs and severity of V1 connectivity deficits provides a neuroanatomic mechanism for these signs. Restoration of binocular fusion and V1 connections after short durations of decorrelation helps explain the benefits of early strabismus repair in humans.

A Shout Out to Immature Synapses. Focus on “Different Roles for AMPA and NMDA Receptors in Transmission at the Immature Retinogeniculate Synapse”

A major topic of investigation in the field of developmental neuroscience is to understand how newly formed excitatory synapses receive and transmit information. It is now widely accepted that neural activity plays an important role in a number of developmental processes, including the refinement and establishment of orderly connections (Grubb and Thompson 2004). However, it remains unclear how many immature excitatory synapses (i.e., ones that utilize glutamate as a neurotransmitter) participate in the relay of activity. Contributing to this problem is the finding that immature glutamatergic synapses are comprised largely of N-methyl-D-aspartate (NMDA) receptors and lack AMPA receptors that mediate fast excitatory transmission. Such synapses are said to be “silent,” incapable of causing postsynaptic action potentials from resting levels because in addition to glutamate, the NMDA receptor requires membrane depolarization to relieve a voltage-dependent Mg 2 block. How then do silent synapses “speak” loudly enough to cause postsynaptic firing and thereby successfully relay information? In a recent article, Liu and Chen (2008) provide some answers to this question. They examine the synaptic responses and intrinsic properties of developing neurons by making use of an in vitro thalamic slice preparation that maintains the excitatory synaptic connections between retinal ganglion cells and relay cells of the dorsal lateral geniculate nucleus (LGN). In an elegant series of whole cell recording experiments, they show how a constellation of properties, including ligand-gated channel kinetics, receptor subunit composition, extended presence of neurotransmitter

Intrinsic-signal optical imaging reveals cryptic ocular dominance columns in primary visual cortex of new world owl monkeys

A significant concept in neuroscience is that sensory areas of the neocortex have evolved the remarkable ability to represent a number of stimulus features within the confines of a global map of the sensory periphery. Modularity, the term often used to describe the inhomogeneous nature of the neocortex, is without a doubt an important organizational principle of early sensory areas, such as the primary visual cortex (V1). Ocular dominance columns, one type of module in V1, are found in many primate species as well as in carnivores. Yet, their variable presence in some New World monkey species and complete absence in other species has been enigmatic. Here, we demonstrate that optical imaging reveals the presence of ocular dominance columns in the superficial layers of V1 of owl monkeys (Aotus trivirgatus), even though the geniculate inputs related to each eye are highly overlapping in layer 4. The ocular dominance columns in owl monkeys revealed by optical imaging are circular in appearance. The distance between left eye centers and right eye centers is approximately 650 μm. We find no relationship between ocular dominance centers and other modular organizational features such as orientation pinwheels or the centers of the cytochrome oxidase blobs. These results are significant because they suggest that functional columns may exist in the absence of obvious differences in the distributions of activating inputs and ocular dominance columns may be more widely distributed across mammalian taxa than commonly suggested.

A temporal frequency–dependent functional architecture in human V1 revealed by high-resolution fMRI

Although cortical neurons with similar functional properties often cluster together in a columnar organization, only ocular dominance columns, the columnar structure representing segregated anatomical input (from one of the two eyes), have been found in human primary visual cortex (V1). It has yet to be shown whether other columnar organizations that arise only from differential responses to stimulus properties also exist in human V1. Using high-resolution functional magnetic resonance imaging, we have found such a functional architecture containing domains that respond preferentially to either low or high temporal frequency.

Subplate neurons and the patterning of thalamocortial connections.

The patterning of the cerebral cortex into functionally distinct domains relies on the formation of appropriate connections between the thalamus and the cortex during development. To identify the mechanisms that underlie cortical target selection by thalamic axons, we have examined the role of cellular interactions in the formation of connections between the lateral geniculate nucleus (LGN) and the visual cortex during development of the cat visual system. The morphology of LGN axons as they grow towards the visual cortex suggests that interactions within the subplate zone may be important in the development of geniculocortical connections. The requirement for subplate neurons in this process was examined by ablating subplate neurons underlying the visual cortex at various developmental stages. When subplate cells are deleted between E38 and E42, prior to target innervation by LGN axons, these axons fail to select the visual cortex as their correct target and instead grow past it, staying restricted to the white matter. Deletion of subplate cells at later stages, between P2 and P7, does not affect target selection, but instead it prevents the segregation of LGN axons into ocular dominance columns within layer IV of the cortex. The effects of subplate neuron ablation suggest that interactions between thalamic axons and subplate cells are of critical importance in the specification of thalamocortical connections during development.

Complete Pattern of Ocular Dominance Columns in Human Primary Visual Cortex

The occipital lobes were obtained after death from six adult subjects with monocular visual loss. Flat-mounts were processed for cytochrome oxidase (CO) to reveal metabolic activity in the primary (V1) and secondary (V2) visual cortices. Mean V1 surface area was 2643 mm2 (range, 1986-3477 mm2). Ocular dominance columns were present in all cases, having a mean width of 863 microm. There were 78-126 column pairs along the V1 perimeter. Human column patterns were highly variable, but in at least one person they resembled a scaled-up version of macaque columns. CO patches in the upper layers were centered on ocular dominance columns in layer 4C, with one exception. In this individual, the columns in a local area resembled those present in the squirrel monkey, and no evidence was found for column/patch alignment. In every subject, the blind spot of the contralateral eye was conspicuous as an oval region without ocular dominance columns. It provided a precise landmark for delineating the central 15 degrees of the visual field. A mean of 53.1% of striate cortex was devoted to the representation of the central 15 degrees. This fraction was less than the proportion of striate cortex allocated to the representation of the central 15 degrees in the macaque. Within the central 15 degrees, each eye occupied an equal territory. Beyond this eccentricity, the contralateral eye predominated, occupying 63% of the cortex. In one subject, monocular visual loss began at age 4 months, causing shrinkage of ocular dominance columns. In V2, which had a larger surface area than V1, CO stripes were present but could not be classified as thick or thin.

Properties of Persistent Postnatal Cortical Subplate Neurons

Subplate (SP) neurons are important for the proper development of thalamocortical innervation. They are necessary for formation of ocular dominance and orientation columns in visual cortex. During the perinatal period, many SP neurons die. The surviving cohort forms interstitial cells in the white matter (WM) and a band of horizontally oriented cells below layer VI (layer VIb, layer VII, or subplate cells). Although the function of embryonic SP neurons has been well established, the functional roles of WM and postnatal SP cells are not known. We used a combination of anatomical, immunohistochemical, and electrophysiological techniques to explore the dendritic morphology, neurotransmitter phenotype, intrinsic electrophysiological, and synaptic input properties of these surviving cells in the rat visual cortex. The density of SP and WM cells significantly decreases during the first month of life. Both populations express neuronal markers and have extensive dendritic arborizations within the SP, WM, and to the overlying visual cortex. Some intrinsic electrophysiological properties of SP and WM cells are similar: each generates high-frequency slowly adapting trains of action potentials in response to a sustained depolarization. However, SP cells exhibit greater frequency-dependent action potential broadening than WM neurons. Both cell types receive predominantly AMPA/kainate receptor-mediated excitatory synaptic input that undergoes paired-pulse facilitation as well as NMDA receptor and GABAergic input. Synaptic inputs to these cells can also undergo long-term synaptic plasticity. Thus, surviving SP and WM cells are functional electrogenic neurons integrated within the postnatal visual cortical circuit.

Intrinsic-signal optical imaging reveals cryptic ocular dominance columns in primary visual cortex of New World owl monkeys.

A significant concept in neuroscience is that sensory areas of the neocortex have evolved the remarkable ability to represent a number of stimulus features within the confines of a global map of the sensory periphery. Modularity, the term often used to describe the inhomogeneous nature of the neocortex, is without a doubt an important organizational principle of early sensory areas, such as the primary visual cortex (V1). Ocular dominance columns, one type of module in V1, are found in many primate species as well as in carnivores. Yet, their variable presence in some New World monkey species and complete absence in other species has been enigmatic. Here, we demonstrate that optical imaging reveals the presence of ocular dominance columns in the superficial layers of V1 of owl monkeys (Aotus trivirgatus), even though the geniculate inputs related to each eye are highly overlapping in layer 4. The ocular dominance columns in owl monkeys revealed by optical imaging are circular in appearance. The distance between left eye centers and right eye centers is approximately 650 mum. We find no relationship between ocular dominance centers and other modular organizational features such as orientation pinwheels or the centers of the cytochrome oxidase blobs. These results are significant because they suggest that functional columns may exist in the absence of obvious differences in the distributions of activating inputs and ocular dominance columns may be more widely distributed across mammalian taxa than commonly suggested.

Robust detection of ocular dominance columns in humans using Hahn Spin Echo BOLD functional MRI at 7 Tesla

Cells in the mammalian brain tend to be grouped together according to their afferent and efferent connectivity, as well as their physiological properties. The columnar structures of neocortex are prominent examples of such modular organization, and have been studied extensively in anatomical and physiological experiments in rats, cats and monkeys. The importance of noninvasive study of such structures, in particular in human subjects, cannot be overemphasized. Not surprisingly, therefore, many attempts were made to map cortical columns using functional magnetic resonance imaging (fMRI). Yet, the robustness, repeatability, and generality of the hitherto used fMRI methodologies have been a subject of intensive debate. Using differential mapping in a high magnetic field magnet (7 T), we demonstrate here the ability of Hahn Spin-Echo (HSE) BOLD to map the ocular dominance columns (ODCs) of the human visual cortex reproducibly over several days with a high degree of accuracy, relative to expected spatial patterns from post-mortem data. On the other hand, the conventional Gradient-Echo (GE) blood oxygen level dependent (BOLD) signal in some cases failed to resolve ODCs uniformly across the selected gray matter region, due to the presence of non-specific signals. HSE signals uniformly resolved the ODC patterns, providing a more generalized mapping methodology (i.e. one that does not require adjusting experimental approaches based on prior knowledge or assumptions about functional organization and vascular structure in order to avoid confounding large vessel effects) to map unknown columnar systems in the human brain, potentially paving the way both for the study of the functional architecture of human sensory cortices, and of brain modules underlying specific cognitive processes.

Modeling self-organizing tri-chromatic color selective regions in primary visual cortex

How does the brain represent and process color in the primary visual cortex (V1)? Experimental evidence from macaque monkey suggests that cells selective for color are organized into small, spatially separated blobs in V1. This organization is strikingly different from that of orientation and ocular dominance maps, which consist of large, spatially contiguous patterns. In this paper, a self-organizing tri-chromatic model of V1 is constructed using natural color image input. Neurons in the modeled V1 are initially unselective, and develop multi-lobed ON/OFF receptive fields through Hebbian learning of retinal responses to visual patterns. The model develops realistic color-selective receptive fields, color maps, ocular dominance columns, and orientation maps. Color-selective blobs are located inside ocular dominance columns, and lateral connections link cells with similar orientation preferences, matching previous experimental results. Further, the model makes a number of predictions for future experiments, including: 1. The color map has three types of color-selective blobs and a unique cortical activation pattern exists for each of the pure color hues. 2. The usual blob-like organization for color emerges as long as the training images have a higher brightness contour gradient compared to the hue contour gradient, and the inputs are highly correlated between the eyes. Otherwise the color blobs regularly extend across borders of ocular dominance stripes (contrary to macaque results). 3. Neurons in areas where red and green patches are near each other respond to both red and green, causing them to maximally prefer yellow, even though there are no yellow photoreceptors in the retina. 4. Cells selective for color connect to other cells with similar chromatic preferences: Blue-selective neurons connect to blue selective neurons, red-selective to other red-selective neurons, and so forth. Thus the model replicates the known data on the organization of color selectivity in V1, gives a detailed explanation for how this structure develops and functions, and provides concrete predictions that can be tested in future experiments. These findings suggest that a single self-organizing system may underlie the development of orientation selectivity, eye preference, color selectivity, and lateral connectivity in the primary visual cortex.

Functional Organization of Color Domains in V1 and V2 of Macaque Monkey Revealed by Optical Imaging

Areas V1 and V2 of Macaque monkey visual cortex are characterized by unique cytochrome-oxidase (CO)-staining patterns. Initial electrophysiological studies associated CO blobs in V1 with processing of surface properties such as color and brightness and the interblobs with contour information processing. However, many subsequent studies showed controversial results, some supporting this proposal and others failing to find significant functional differences between blobs and interblobs. In this study, we have used optical imaging to map color-selective responses in V1 and V2. In V1, we find striking "blob-like" patterns of color response. Fine alignment of optical maps and CO-stained tissue revealed that color domains in V1 strongly associate with CO blobs. We also find color domains in V1 align along centers of ocular dominance columns. Furthermore, color blobs in V1 have low orientation selectivity and do not overlap with centers of orientation domains. In V2, color domains coincide with thin stripes; orientation-selective domains coincide with thick and pale stripes. We conclude that color and orientation-selective responses are preferentially located in distinct CO compartments in V1 and V2. We propose that the term "blob" encompasses both the concept of "CO blob" and "color domain" in V1.

The Effect of Angioscotomas on Map Structure in Primary Visual Cortex

When blood vessels occlude the photoreceptor layer in the retina, they cast shadows onto the photoreceptors, creating angioscotomas (regions of the visual field to which that eye is blind). Remarkably, Adams and Horton (2002) have recently shown that it is sometimes possible to observe representations of these angioscotomas anatomically in the primary visual cortices of squirrel monkeys. However, there is substantial variability in the degree and form of these representations. The source of this variability is difficult to determine experimentally, because experimental studies are unavoidably limited by small sample size. In addition, experimental studies cannot compare the map structure that would develop with and without an angioscotoma. Here, we investigate these phenomena computationally using feature-mapping models of visual cortical development, which are not subject to the same limitations. These models suggest that the primary source of variability in angioscotoma representation is the precise timing of the onset of visual experience relative to the time course of ocular dominance column segregation. Furthermore, the models predict that angioscotomas could compete for control of local column layout with other influences such as cortical shape but that they have a small effect on the structure of orientation preference maps.

Local Potential Connectivity in Cat Primary Visual Cortex

Time invariant description of synaptic connectivity in cortical circuits may be precluded by the ongoing growth and retraction of dendritic spines accompanied by the formation and elimination of synapses. On the other hand, the spatial arrangement of axonal and dendritic branches appears stable. This suggests that an invariant description of connectivity can be cast in terms of potential synapses, which are locations in the neuropil where an axon branch of one neuron is proximal to a dendritic branch of another neuron. In this paper, we attempt to reconstruct the potential connectivity in local cortical circuits of the cat primary visual cortex (V1). Based on multiple single-neuron reconstructions of axonal and dendritic arbors in 3 dimensions, we evaluate the expected number of potential synapses and the probability of potential connectivity among excitatory (pyramidal and spiny stellate) neurons and inhibitory basket cells. The results provide a quantitative description of structural organization of local cortical circuits. For excitatory neurons from different cortical layers, we compute local domains, which contain their potentially pre- and postsynaptic excitatory partners. These domains have columnar shapes with laminar specific radii and are roughly of the size of the ocular dominance column. Therefore, connections between most excitatory neurons in the ocular dominance column can be implemented by local synaptogenesis. Structural connectivity involving inhibitory basket cells is generally weaker than excitatory connectivity. Here, only nearby neurons are capable of establishing more than one potential synapse, implying that within the ocular dominance column these connections have more limited potential for circuit remodeling.

Micro-field evoked potentials recorded from the porcine sub-dural cortical surface utilizing a microelectrode array

A sub-dural surface microelectrode array designed to detect micro-field evoked potentials has been developed. The device is comprised of an array of 350-μm square gold contacts, with bidirectional spacing of 150μm, contained within a polyimide Kapton material. Cytotoxicity testing suggests that the device is suitable for use with animal and human patients. Implementation of the device in animal studies revealed that reliable evoked potentials could be acquired. Further work will be needed to determine how these micro-field potentials, which demonstrate selectivity for one eye, relate to the distribution of the ocular dominance columns of the occipital cortex.

Mapping Iso-Orientation Columns by Contrast Agent-Enhanced Functional Magnetic Resonance Imaging: Reproducibility, Specificity, and Evaluation by Optical Imaging of Intrinsic Signal

Activation resembling ocular dominance or orientation columns has been mapped with high-resolution functional magnetic resonance imaging (fMRI). However, the neuronal interpretation of these functional maps is unclear because of the poor sensitivity of fMRI, unknown point spread function (PSF), and lack of comparison with independent techniques. Here we show that cerebral blood volume (CBV)-weighted fMRI with a blood plasma contrast agent (monocrystalline iron oxide nanoparticles), in combination with continuous temporally encoded stimulation, can map columnar neuronal activity in the cat primary visual cortex with high sensitivity, selectivity, and reproducibility. We examined hemodynamic response PSF by comparing these CBV-based signals with oxygen metabolism-based negative blood oxygenation level-dependent signals. A significant positive correlation exists between CBV- and metabolism-based iso-orientation maps, suggesting that the hemodynamic PSF is narrower than intercolumn distances. We also compared CBV-based fMRI with optical intrinsic signal (OIS) imaging, a technique that identifies sites of increased neuronal activity, to investigate neuronal correlation. Iso-orientation maps obtained by fMRI and OIS were well matched, indicating that areas of the highest orientation-selective CBV signals correspond to sites of increased neural activity. Using CBV-based fMRI, we successfully mapped orientation-selective functional architecture in the medial bank of the visual cortex, an area inaccessible to OIS imaging. Thus, we conclude that contrast agent-based fMRI, in combination with continuous temporally encoded stimulation, is a highly sensitive technique capable of mapping neural activity at the resolution of functional columns without depth limitation.

Spontaneous Retinal Activity Mediates Development of Ocular Dominance Columns and Binocular Receptive Fields in V1

The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex.

Early Retinal Activity and Visual Circuit Development

Does spontaneous retinal activity prior to vision play a role in the establishment of visual maps? In this issue of Neuron, two separate papers by Huberman et al. and Hooks and Chen demonstrate a role for early spontaneous retinal activity in the establishment of ocular dominance columns and synaptic refinement at retinogeniculate synapses.

Ocular integration in the human visual cortex

Human striate cortex contains an orderly map of the contralateral visual field, which is distorted to make a disproportionate amount of tissue available for the representation of the macula. Engrafted on the retinotopic map is a system of alternating inputs known as ocular dominance columns. These columns consist of interleaved bands of geniculocortical afferents in layer 4C serving either the right eye or the left eye.They can be revealed in humans with a history of prior visual loss in one eye by processing striate cortex for cytochrome oxidase at autopsy. Because their geniculate input is segregated, cells within ocular dominance columns in layer 4C respond to stimulation of one eye only.These monocular cells converge onto binocular cells in other layers, integrating signals from the two eyes. The columns in humans appear similar to those found in many primate species, including the macaque. In the squirrel monkey, however, the occurrence of ocular dominance columns is highly variable. Some squirrel monkeys lack columns, yet they seem to have no impairment of visual function. In animals with weakly expressed columns, one can detect a cortical pattern of metabolic activity corresponding to retinal blood vessels. It appears because visual deprivation from shadows cast by blood vessels induces remodeling of geniculocortical afferents, in a manner akin to the shrinkage of ocular dominance columns from congenital cataract. Although the function of ocular dominance columns is unknown, their metabolism is altered in strabismus, suggesting a role in visual suppression.

Distribution of calbindin-28kD and parvalbumin in V1 in normal adult Cebus apella monkeys and in monkeys with retinal lesions

Several proteins have their normal patterns of distributions altered by monocular visual deprivation. We studied the distribution of the calcium-binding proteins calbindin-28kD (Cb) and parvalbumin (Pv) in V1 in normal adult Cebus apella monkeys and in monkeys with monocular retinal lesions. In normal monkeys, the interblobs regions in layers 2/3 and the layer 4B are intensely labeled for Cb, while Pv reaction showed a complementary labeling pattern with a stronger staining in layers 4A, 4C and in the blob regions in layers 2/3. In monkeys with monocular retinal lesion, the laminar distribution of these proteins was differentially affected, although both reactions resulted in stronger labeling in non-deprived ocular dominance columns. While Cb reaction resulted in stronger labeling in layers 1 through 5, Pv labeling was heavier in layers 2/3, 4A and 4C. There was a clear reduction in the intensity of neuropil staining for both Pv and Cb in deprived ocular dominance columns with little or no reduction in number of labeled cells. This reduction could thus be attributed to activity-dependent changes at synapses level.

Subplate Neurons Regulate Maturation of Cortical Inhibition and Outcome of Ocular Dominance Plasticity

Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.