Orientation Columns Research Articles

Interareal coordination of columnar architectures during visual cortical development

The formation of cortical columns is often conceptualized as a local process in which synaptic microcircuits confined to the volume of the emerging column are established and selectively refined. Many neurons, however, while wiring up locally are simultaneously building macroscopic circuits spanning widely distributed brain regions, such as different cortical areas or the two brain hemispheres. Thus, it is conceivable that interareal interactions shape the local column layout. Here we show that the columnar architectures of different areas of the cat visual cortex in fact develop in a coordinated manner, not adequately described as a local process. This is revealed by comparing the layouts of orientation columns (i) in left/right pairs of brain hemispheres and (ii) in areas V1 and V2 of individual brain hemispheres. Whereas the size of columns varied strongly within all areas considered, columns in different areas were typically closely matched in size if they were mutually connected. During development, we find that such mutually connected columns progressively become better matched in size as the late phase of the critical period unfolds. Our results suggest that one function of critical-period plasticity is to progressively coordinate the functional architectures of different cortical areas--even across hemispheres.

Metaplasticity Governs Natural Experience-Driven Plasticity of Nascent Embryonic Brain Circuits

During embryogenesis, brain neurons receiving the same sensory input may undergo potentiation or depression. While the origin of variable plasticity in vivo is unknown, it plays a key role in shaping dynamic neural circuit refinement. Here, we investigate effects of natural visual stimuli on neuronal firing within the intact, awake, developing brain using calcium imaging of 100 s of central neurons in the Xenopus retinotectal system. We find that specific patterns of visual stimuli shift population responses toward either potentiation or depression in an N-methyl-D-aspartate receptor (NMDA-R)-dependent manner. In agreement with Bienenstock-Cooper-Munro metaplasticity, our results show that functional potentiation or depression can be predicted by individual neurons' specific receptive field properties and historic firing rates. Interestingly, this activity-dependent metaplasticity is itself NMDA-R dependent. Furthermore, network analysis reveals increased correlated firing of neurons that undergo potentiation. These findings implicate metaplasticity as a natural property regulating experience-dependent refinement of nascent embryonic brain circuits.

High-field fMRI unveils orientation columns in humans

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90 degrees (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.

Comparing the feature selectivity of the gamma-band of the local field potential and the underlying spiking activity in primate visual cortex

The local field potential (LFP), comprised of low-frequency extra-cellular voltage fluctuations, has been used extensively to study the mechanisms of brain function. In particular, oscillations in the gamma-band (30–90 Hz) are ubiquitous in the cortex of many species during various cognitive processes. Surprisingly little is known about the underlying biophysical processes generating this signal. Here, we examine the relationship of the local field potential to the activity of localized populations of neurons by simultaneously recording spiking activity and LFP from the primary visual cortex (V1) of awake, behaving macaques. The spatial organization of orientation tuning and ocular dominance in this area provides an excellent opportunity to study this question, because orientation tuning is organized at a scale around one order of magnitude finer than the size of ocular dominance columns. While we find a surprisingly weak correlation between the preferred orientation of multi-unit activity and gamma-band LFP recorded on the same tetrode, there is a strong correlation between the ocular preferences of both signals. Given the spatial arrangement of orientation tuning and ocular dominance, this leads us to conclude that the gamma-band of the LFP seems to sample an area considerably larger than orientation columns. Rather, its spatial resolution lies at the scale of ocular dominance columns.

Evidence for corticocortical connections between areas 7 and 17 in cerebral cortex of the cat

This study provides the first evidence of direct corticocortical connections between areas 7 and 17 of the cat. Wheat germ agglutinin horseradish peroxidase (WGA-HRP) was administrated by micro-electrophoresis and micro-injection, respectively, into area 17 and area 7 in different hemispheres in eight cats. WGA-HRP labeled pyramidal neurons were observed primarily in layer 5 of areas 7 and 17 indicating that there are reciprocal connections between these areas. Optical imaging was used to guide WGA-HRP injections to single orientation columns in area 17. After such restricted injections labeled pyramidal cells were observed in layer 5 of area 7. These pyramidal cells were arranged as discontinuous patches extending across a broad region of area 7. These results suggest that feedback from area 7 to area 17 may arise from specific functional columns in area 7.

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.

Structure of the neuronal interactions underlying human contour integration

Contour integration is believed to be an important step in human image processing and object recognition, and has been shown to be performed very efficiently by the visual system. However, its neuronal mechanisms are still not well understood. Most contour integration models propose lateral connections between distant orientation columns of similar orientation preference for establishing a so-called 'association field', which links colinearily aligned edge elements into a single contour. However, these models differ both in their dynamics and structure. In some models, afferent input from visual stimuli and lateral input are summed up, in other models these quantities are multiplied. In addition, one finds different assumptions on the range, geometry, and symmetry of the lateral connectivity. It is often assumed that long-range horizontal interactions in V1 serve as the neuronal substrate for the association field. Probabilistic models require unidirectional lateral interactions, linking orientation columns in only one direction, in order to get optimal contour detection performance. In contrast, experimental findings in monkeys rather suggest isotropic connections, spreading symmetrically into all directions from an orientation column. In order to analyze the range and symmetry of lateral interactions underlying contour integration in the human brain, we compared simulations of multiplicative and additive model dynamics with psychophysical contour detection data. For these investigations we used stimuli generated from association fields with different geometries. As expected, models detect contours exceedingly well when using the same association field for contour generation and contour detection. However, analyzing the correlations between human behavior and model prediction on a trial-by-trial basis showed that human behavior is reproduced best, when using the same association field for all contour geometries. Furthermore it turned out that a bidirectional association field reaching only to the nearest neighboring edge elements can not explain the correlations found among the responses of different subjects, while a single unidirectional association field can do so. However, when assuming connections up to the next to-nearest-neighbor elements, a bidirectional association field also explains the correlations between human subjects. The stimuli were designed such that the distance between two neighboring elements lies within the range of long-range connections found in V1. Hence our results allow two possible conclusions: If contour integration relies on horizontal interactions of the spatial range like in V1, a so far unknown unidirectional linking mechanism between neuronal columns is required. If such a unidirectional mechanism does not exist, our results suggest that contour integration is based on interactions on a larger spatial scale as found in higher cortical areas.

Dense gap-junction connections support dynamic Turing structures in the cortex

The recent report by Fukuda et al [1] provides convincing evidence for dense gap-junction connectivity between inhibitory neurons in the cat visual cortex, each neuron making 60 +/- 12 gap-junction dendritic connections with neurons in both the same and adjoining orientation columns. These resistive connections provide a source of diffusive current to the receiving neuron, supplementing the chemical-synaptic currents generated by incoming action-potential spike activity. Fukuda et al describe how the gap junctions form a dense and homogeneous electrical coupling of interneurons, and propose that this diffusion-coupled network provides the substrate for synchronization of neuronal populations. To date, large-scale population-based mathematical models of the cortex have ignored diffusive communication between neurons. Here we augment a well-established mean-field cortical model [2] by incorporating gap-junction-mediated diffusion currents, and we investigate the implications of strong diffusive coupling. The significant result is the model prediction that the 2D cortex can spontaneously generate centimetre-scale Turing structures (spatial patterns), in which regions of high-firing activity are intermixed with regions of low-firing activity (see Fig. ​Fig.1).1). Since coupling strength decreases with increases in firing rate, these patterns are expected to exchange contrast on a slow time-scale, with low-firing patches increasing their activity at the expense of high-firing patches. These theoretical predictions are consistent with the slowly fluctuating large-scale brain-activity images detected from the BOLD (blood oxygen-level-dependent) signal [3]. Figure 1 Diffusion-induced Turing patterns in a square cortex of side 25 cm. Panel a shows the case of zero diffusion: the cortex organizes into a diffuse, cloud-like pattern, but fails to generate a Turing structure. Panels b-d show increasing inhibitory diffusion. ...

Neural Interpretation of Blood Oxygenation Level-Dependent fMRI Maps at Submillimeter Columnar Resolution

Whether conventional gradient-echo (GE) blood oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is able to map submillimeter-scale functional columns remains debatable mainly because of the spatially nonspecific large vessel contribution, poor sensitivity and reproducibility, and lack of independent evaluation. Furthermore, if the results from optical imaging of intrinsic signals are directly applicable, regions with the highest BOLD signals may indicate neurally inactive domains rather than active columns when multiple columns are activated. To examine these issues, we performed BOLD fMRI at a magnetic field of 9.4 tesla to map orientation-selective columns of isoflurane-anesthetized cats. We could not convincingly map orientation columns using conventional block-design stimulation and differential analysis method because of large fluctuations of signals. However, we successfully obtained GE BOLD iso-orientation maps with high reproducibility (r = 0.74) using temporally encoded continuous cyclic orientation stimulation with Fourier data analysis, which reduces orientation-nonselective signals such as draining artifacts and is less sensitive to signal fluctuations. We further reduced large vessel contribution using the improved spin-echo (SE) BOLD method but with overall decreased sensitivity. Both GE and SE BOLD iso-orientation maps excluding large pial vascular regions were significantly correlated to maps with a known neural interpretation, which were obtained in contrast agent-aided cerebral blood volume fMRI and total hemoglobin-based optical imaging of intrinsic signals at a hemoglobin iso-sbestic point (570 nm). These results suggest that, unlike the expectation from deoxyhemoglobin-based optical imaging studies, the highest BOLD signals are localized to the sites of increased neural activity when column-nonselective signals are suppressed.

The Emergence of Contrast-Invariant Orientation Tuning in Simple Cells of Cat Visual Cortex

Simple cells in primary visual cortex exhibit contrast-invariant orientation tuning, in seeming contradiction to feed-forward models that rely on lateral geniculate nucleus (LGN) input alone. Contrast invariance has therefore been thought to depend on the presence of intracortical lateral inhibition. In vivo intracellular recordings instead suggest that contrast invariance can be explained by three properties of the excitatory pathway. (1) Depolarizations evoked by orthogonal stimuli are determined by the amount of excitation a cell receives from the LGN, relative to the excitation it receives from other cortical cells. (2) Depolarizations evoked by preferred stimuli saturate at lower contrasts than the spike output of LGN relay cells. (3) Visual stimuli evoke contrast-dependent changes in trial-to-trial variability, which lead to contrast-dependent changes in the relationship between membrane potential and spike rate. Thus, high-contrast, orthogonally oriented stimuli that evoke significant depolarizations evoke few spikes. Together these mechanisms, without lateral inhibition, can account for contrast-invariant stimulus selectivity.

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.

Independent component analysis of high-resolution imaging data identifies distinct functional domains

In the vertebrate brain external stimuli are often represented in distinct functional domains distributed across the cortical surface. Fast imaging techniques used to measure patterns of population activity record movies with many pixels and many frames, i.e., data sets with high dimensionality. Here we demonstrate that principal component analysis (PCA) followed by spatial independent component analysis (sICA), can be exploited to reduce the dimensionality of data sets recorded in the olfactory bulb and the somatosensory cortex of mice as well as the visual cortex of monkeys, without loosing the stimulus-specific responses. Different neuronal populations are separated based on their stimulus-specific spatiotemporal activation. Both, spatial and temporal response characteristics can be objectively obtained, simultaneously. In the olfactory bulb, groups of glomeruli with different response latencies can be identified. This is shown for recordings of olfactory receptor neuron input measured with a calcium-sensitive axon tracer and for network dynamics measured with the voltage-sensitive dye RH 1838. In the somatosensory cortex, barrels responding to the stimulation of single whiskers can be automatically detected. In the visual cortex orientation columns can be extracted. In all cases artifacts due to movement, heartbeat or respiration were separated from the functional signal by sICA and could be removed from the data set. sICA following PCA is therefore a powerful technique for data compression, unbiased analysis and dissection of imaging data of population activity, collected with high spatial and temporal resolution.

The Radial Bias: A Different Slant on Visual Orientation Sensitivity in Human and Nonhuman Primates

It is generally assumed that sensitivity to different stimulus orientations is mapped in a globally equivalent fashion across primate visual cortex, at a spatial scale larger than that of orientation columns. However, some evidence predicts instead that radial orientations should produce higher activity than other orientations, throughout visual cortex. Here, this radial orientation bias was robustly confirmed using (1) human psychophysics, plus fMRI in (2) humans and (3) behaving monkeys. In visual cortex, fMRI activity was at least 20% higher in the retinotopic representations of polar angle which corresponded to the radial stimulus orientations (relative to tangential). In a global demonstration of this, we activated complementary retinotopic quadrants of visual cortex by simply changing stimulus orientation, without changing stimulus location in the visual field. This evidence reveals a neural link between orientation sensitivity and the cortical retinotopy, which have previously been considered independent.

Instructive Effect of Visual Experience in Mouse Visual Cortex

We describe a form of experience-dependent response enhancement in the visual cortex of awake mice. Repeated presentations of grating stimuli of a single orientation result in a persistent enhancement of responses evoked by the test stimulus. Response potentiation is specific to the orientation of the test stimulus, develops gradually over the course of several training sessions, and occurs in both juvenile and adult mice. The stimulus-selective response potentiation (SRP) can mask deprivation-induced response depression in adult mice. SRP requires NMDA receptor activation and is prevented by viral delivery of a peptide that interferes with AMPA receptor trafficking. SRP may reveal the mechanisms involved in certain forms of perceptual learning.

Slab-like functional architecture of higher order cortical area 21a showing oblique effect of orientation preference in the cat

Optical imaging based on intrinsic signals is a powerful tool for in vivo studying functional organization of various cortices. Here, the functional architecture of orientation-sensitive neurons in higher order extrastriate cortical area 21a was investigated in cats using optical imaging combined with electrophysiological methods. It is found that neurons in area 21 with similar preferred orientations were functionally organized into a slab-like columnar structure orthogonal to the cortical surface, and the orientation columns were distributed more densely than those in area 17. The responsiveness and activated areas of optical maps visually elicited by the horizontal and vertical gratings were always larger than those by oblique gratings in areas 21a and 17. This neural oblique effect shown in orientation maps was more significant in area 21a than that in area 17. The findings suggest a neuronal mechanism in the higher order extrastriate cortex involving the visual perceptive process of the superiority of cardinal contours.

Gap Junctions among Dendrites of Cortical GABAergic Neurons Establish a Dense and Widespread Intercolumnar Network

Gap junctions are common between cortical GABAergic interneurons but little is known about their quantitative distribution along dendritic profiles. Here, we provide direct morphological evidence that parvalbumin-containing GABAergic neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks through dendritic gap junctions. Gap junction-coupled networks of parvalbumin neurons were visualized using connexin36 immunohistochemistry and confocal laser-scanning microscopy (CLSM). The direct correspondence of connexin36-immunopositve puncta and gap junctions was confirmed by examining the same structures in both CLSM and electron microscopy. Single parvalbumin neurons with large somata (> or =200 microm2) formed 60.3 +/- 12.2 (mean +/- SD) gap junctions with other cells whereby these contacts were not restricted to proximal dendrites but occurred at distances of up to 380 microm from the soma. In a Sholl analysis of large-type parvalbumin neurons, 21.9 +/- 7.9 gap junctions were within 50 microm of the soma, 21.7 +/- 7.6 gap junctions in a segment between 50 and 100 microm, 11.2 +/- 4.7 junctions between 100 and 150 microm, and 5.6 +/- 3.6 junctions were in more distal segments. Serially interconnected neurons could be traced laterally in a boundless manner through multiple gap junctions. Comparison to the orientation-preference columns revealed that parvalbumin-immunoreactive cells distribute randomly whereby their large dendritic fields overlap considerably and cover different orientation columns. It is proposed that this dense and homogeneous electrical coupling of interneurons supports the precise synchronization of neuronal populations with differing feature preferences thereby providing a temporal frame for the generation of distributed representations.

Orientation selectivity in the common marmoset ( Callithrix jacchus): The periodicity of orientation columns in V1 and V2

Orientation selectivity is a ubiquitous property of the primary visual cortex of mammals. Within the primate, orientation selectivity is arranged into vertical columns that are organized into a regular patchy pattern. Previous studies, in old world primates, have noted an anisotropy in this arrangement that appears to be due to the presence of ocular dominance columns within the same tissue. In addition, orientation selective responses appear to be arranged into bands of activity within the adjoining extrastriate region V2. Little is known about the precise arrangement of orientation columns within V2. In this study, we examined the layout of orientation columns within both V1 and V2 of a new world primate, the common marmoset, using optical imaging. New world primates have the advantage that, unlike the macaque, V2 exists on the cortical surface, a requirement for this form of optical mapping. We found the arrangement of orientation columns to be isotropic within marmoset V1 with an average repeat distance of around 575 μm, smaller than the repeat distance previously reported for the macaque. We found no evidence of ocular dominance within the animals tested supporting the claim that ocular dominance columns when present distort the mapping of orientation in V1. In V2 we found that orientation columns were larger and as in other primates were represented in discrete bands throughout V2. Orientation columns were spaced on average around 1 mm apart. This suggests that, at least in the marmoset, the visual system maps orientation at a different scale within V1 and V2.

A very different slant on orientation sensitivity in human and non-human primates

It is generally assumed that sensitivity to different stimulus orientations is mapped in a globally equivalent fashion across primate visual cortex, at a spatial scale larger than that of orientation columns. However earlier evidence, and a new model, predicts instead that radial orientations should produce higher activity than other orientations, throughout visual cortex. Here this prediction was robustly confirmed using human psychophysics, human fMRI, and fMRI in behaving macaque monkeys. In both human and macaque cortex, fMRI activity was higher in the retinotopic representations of polar angle which corresponded to the radial stimulus orientations. In a global demonstration of this, we activated complementary retinotopic quadrants of visual cortex by simply changing stimulus orientation - without changing the stimulus location in the visual field. This radial bias was also robust in psychophysical tests, using analogous stimuli. All this evidence confirms a novel link between orientation sensitivity and the cortical retinotopy, which have previously been considered independent.

Evidence indicating that pre-migraine CSD can begin in either V1 or V2, and cross a border into the other

The visual aura that often precedes migraine has been generally accepted as due to Cortical Spreading Depression, or CSD, and previously thought to be limited to V1. The author has precisely documented over 350 aura episodes over 10 years, which have revealed repeating origin locations and patterns. First, a scintillating “fortification” scotoma (assumed due to crossing of orientation columns) indicates “brushfire” coverage of most of V1, although some smaller areas have never been crossed, and one small area doubles back. Second, when a later episode begins at the same visual (or cortical) origin, they have identical progression patterns, even if observed years apart, indicating a fixed relationship to topography of the calcarine sulcus. Also, there have been more subtle observations of auxiliary negative scotoma without scintillations, indicating a V2 location. As either type of scotoma progression approaches the visual vertical meridian, it appears to “bounce” back from the meridian, while it changes from one scotoma mode to the other. This seems to be visual evidence of the CSD crossing the V1/V2 borders between striate and non-striate cortex, or from V2v through V1 to V2d.

Spontaneous symmetry breaking in self–organizing neural fields

We extend the theory of self-organizing neural fields in order to analyze the joint emergence of topography and feature selectivity in primary visual cortex through spontaneous symmetry breaking. We first show how a binocular one-dimensional topographic map can undergo a pattern forming instability that breaks the underlying symmetry between left and right eyes. This leads to the spatial segregation of eye specific activity bumps consistent with the emergence of ocular dominance columns. We then show how a 2-dimensional isotropic topographic map can undergo a pattern forming instability that breaks the underlying rotation symmetry. This leads to the formation of elongated activity bumps consistent with the emergence of orientation preference columns. A particularly interesting property of the latter symmetry breaking mechanism is that the linear equations describing the growth of the orientation columns exhibits a rotational shift-twist symmetry, in which there is a coupling between orientation and topography. Such coupling has been found in experimentally generated orientation preference maps.