The development and activity-dependent expression of aggrecan in the cat visual cortex.

The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus (dLGN). During development, aggrecan expression increases in the dLGN with a time course that matches the decline in plasticity. Moreover, examination of tissue from selectively visually deprived cats shows that expression is activity dependent, suggesting a role for aggrecan in the termination of the sensitive period. Here, we demonstrate for the first time that the onset of aggrecan expression in area 17 also correlates with the decline in experience-dependent plasticity in visual cortex and that this expression is experience dependent. Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan-positive neurons in the extragranular layers, but not in layer IV. This effect was reversible as dark-reared animals that were subsequently exposed to light showed normal numbers of Cat-301-positive cells. The reduction in aggrecan following certain early deprivation regimens is the first biochemical correlate of the functional changes to the γ-aminobutyric acidergic system that have been reported following early deprivation in cats.

Cortical plasticity: learning while you sleep?

Sleep has been suggested to facilitate memory consolidation or learning, but there has been little direct evidence of a link between synaptic plasticity and sleep. A recent study suggests a role for sleep in the plastic changes that the visual cortex undergoes in response to occlusion of one eye early in life.

An analysis of orientation and ocular dominance patterns in the visual cortex of cats and ferrets.

We report an analysis of orientation and ocular dominance maps that were recorded optically from area 17 of cats and ferrets. Similar to a recent study performed in primates (Obermayer & Blasdel, 1997), we find that 80% (for cats and ferrets) of orientation singularities that are nearest neighbors have opposite sign and that the spatial distribution of singularities deviates from a random distribution of points, because the average distances between nearest neighbors are significantly larger than expected for a random distribution. Orientation maps of normally raised cats and ferrets show approximately the same typical wavelength; however, the density of singularities is higher in ferrets than in cats. Also, we find the well-known overrepresentation of cardinal versus oblique orientations in young ferrets (Chapman & Bonhoeffer, 1998; Coppola, White, Fitzpatrick, & Purves, 1998) but only a weak, not quite significant overrepresentation of cardinal orientations in cats, as has been reported previously (Bonhoeffer & Grinvald, 1993). Orientation and ocular dominance slabs in cats exhibit a tendency of being orthogonal to each other (Hubener, Shoham, Grinvald, & Bonhoeffer, 1997), albeit less pronounced, as has been reported for primates (Obermayer & Blasdel, 1993). In chronic recordings from single animals, a decrease of the singularity density and an increase of the ocular dominance wavelength with age but no change of the orientation wavelengths were found. Orientation maps are compared with two pattern models for orientation preference maps: bandpass-filtered white noise and the field analogy model. Bandpass-filtered white noise predicts sign correlations between orientation singularities, but the correlations are significantly stronger (87% opposite sign pairs) than what we have found in the data. Also, bandpass-filtered noise predicts a deviation of the spatial distribution of singularities from a random dot pattern. The field analogy model can account for the structure of certain local patches but not for the whole orientation map. Differences between the predictions of the field analogy model and experimental data are smaller than what has been reported for primates (Obermayer & Blasdel, 1997), which can be explained by the smaller size of the imaged areas in cats and ferrets.

An alternative view of perceptual rivalry.

The mechanism by which one or the other view of an ambiguous figure - such as the Necker cube - gains dominance has been unclear. Recent evidence suggests that the right frontoparietal cortex is responsible for the selection process, and that each cortical hemisphere represents one of the two rivalling percepts.

Principal component analysis and blind separation of sources for optical imaging of intrinsic signals.

The analysis of data sets from optical imaging of intrinsic signals requires the separation of signals, which accurately reflect stimulated neuronal activity (mapping signal), from signals related to background activity. Here we show that blind separation of sources by extended spatial decorrelation (ESD) is a powerful method for the extraction of the mapping signal from the total recorded signal. ESD is based on the assumptions (i) that each signal component varies smoothly across space and (ii) that every component has zero cross-correlation functions with the other components. In contrast to the standard analysis of optical imaging data, the proposed method (i) is applicable to nonorthogonal stimulus-conditions, (ii) can remove the global signal, blood-vessel patterns, and movement artifacts, (iii) works without ad hoc assumptions about the data structure in the frequency domain, and (iv) provides a confidence measure for the signals (Z score). We first demonstrate on orientation maps from cat and ferret visual cortex, that principal component analysis, which acts as a preprocessing step to ESD, can already remove global signals from image stacks, as long as data stacks for at least two-not necessarily orthogonal-stimulus conditions are available. We then show that the full ESD analysis can further reduce global signal components and-finally-concentrate the mapping signal within a single component both for differential image stacks and for image stacks recorded during presentation of a single stimulus.

Influence of experience on orientation maps in cat visual cortex.

Experience is known to affect the development of ocular dominance maps in visual cortex, but it has remained controversial whether orientation preference maps are similarly affected by limiting visual experience to a single orientation early in life. Here we used optical imaging based on intrinsic signals to show that the visual cortex of kittens reared in a striped environment responded to all orientations, but devoted up to twice as much surface area to the experienced orientation as the orthogonal one. This effect is due to an instructive role of visual experience whereby some neurons shift their orientation preferences toward the experienced orientation. Thus, although cortical orientation maps are remarkably rigid in the sense that orientations that have never been seen by the animal occupy a large portion of the cortical territory, visual experience can nevertheless alter neuronal responses to oriented contours.

Visual attention: spotlight on the primary visual cortex.

Visual search tasks appear to involve spatially selective attention to the target, but evidence for attentional modulation in the visual area with the most precise retinotopic organization V1 has been elusive. Recent imaging studies show that spatial attention can indeed enhance visual responses in human V1.

Different mechanisms underlie three inhibitory phenomena in cat area 17.

Recently, it has been proposed that all suppressive phenomena observed in the primary visual cortex (V1) are mediated by a single mechanism, involving inhibition by pools of neurons, which, between them, represent a wide range of stimulus specificities. The strength of such inhibition would depend on the stimulus that produces it (particularly its contrast) rather than on the firing rate of the inhibited cell. We tested this hypothesis by measuring contrast-response functions (CRFs) of neurons in cat V1 for stimulation of the classical receptive field of the dominant eye with an optimal grating alone, and in the presence of inhibition caused by (1) a superimposed orthogonal grating (cross-orientation inhibition); (2) a surrounding iso-oriented grating (surround inhibition); and (3) an orthogonal grating in the other eye (interocular suppression). We fitted hyperbolic ratio functions and found that the effect of cross-orientation inhibition was best described as a rightward shift of the CRF ('contrast-gain control'), while surround inhibition and interocular suppression were primarily characterised as downward shifts of the CRF ('response-gain control'). However, the latter also showed a component of contrast-gain control. The two modes of suppression were differently distributed between the layers of cortex. Response-gain control prevailed in layer 4, whereas cells in layers 2/3, 5 and 6 mainly showed contrast-gain control. As in human observers, surround gratings caused suppression when the central grating was of high contrast, but in over a third of the cells tested, enhanced responses for low-contrast central stimuli, hence actually decreasing threshold contrast.

Intrinsic and environmental factors in the development of functional maps in cat visual cortex.

In the mammalian visual cortex, key neuronal response properties such as orientation preference and ocular dominance (OD) are mapped in an orderly fashion across the cortical surface. It has been known for some time that manipulating early postnatal visual experience can change the appearance of the OD map. Similar evidence for developmental plasticity of the orientation map has been scarce. We employed optical imaging of intrinsic signals to examine the contribution of intrinsic and environmental factors to the development of cortical maps, using the paradigms of strabismus, reverse occlusion and rearing in a single-orientation environment ('stripe-rearing'). For several weeks after induction of strabismus, the pattern of OD domains remained stable in young kittens. The isotropic magnification of the OD map matched the postnatal growth of the visual cortical surface during the same period. In reverse-occluded and in stripe-reared kittens, orientation preference maps obtained through the left and the right eye were very similar, although the two eyes had never shared any visual experience. We suggest that the geometry of functional maps in the visual cortex is intrinsically determined, while the relative strength of representation of different response properties can be modified through visual experience.

The 'Ideal Homunculus': decoding neural population signals.

Information processing in the nervous system involves the activity of large populations of neurons. It is possible, however, to interpret the activity of relatively small numbers of cells in terms of meaningful aspects of the environment. 'Bayesian inference' provides a systematic and effective method of combining information from multiple cells to accomplish this. It is not a model of a neural mechanism (neither are alternative methods, such as the population vector approach) but a tool for analysing neural signals. It does not require difficult assumptions about the nature of the dimensions underlying cell selectivity, about the distribution and tuning of cell responses or about the way in which information is transmitted and processed. It can be applied to any parameter of neural activity (for example, firing rate or temporal pattern). In this review, we demonstrate the power of Bayesian analysis using examples of visual responses of neurons in primary visual and temporal cortices. We show that interaction between correlation in mean responses to different stimuli (signal) and correlation in response variability within stimuli (noise) can lead to marked improvement of stimulus discrimination using population responses.

Characteristics of surround inhibition in cat area 17.

The effects of stimuli falling outside the 'classical receptive field' and their influence on the orientation selectivity of cells in the cat primary visual cortex are still matters of debate. Here we examine the variety of effects of such peripheral stimuli on responses to stimuli limited to the receptive field. We first determined the extent of the classical receptive field by increasing the diameter of a circular patch of drifting grating until the response saturated or reached a maximum, and by decreasing the diameter of a circular mask in the middle of an extended grating, centred on the receptive field, until the cell just began to respond. These two estimates always agreed closely. We then presented an optimum grating of medium-to-high contrast filling the classical receptive field while stimulating the surround with a drifting grating that had the same parameters as the central stimulus but was varied in orientation. For all but five neurons (of 37 tested), surround stimulation produced clear suppression over some range of orientations, while none showed explicit facilitation under these conditions. For 11 cells (34% of those showing suppression), the magnitude of suppression did not vary consistently with the orientation of the surround stimulus. In the majority of cells, suppression was weakest for a surround grating oriented orthogonal to the cell's optimum. Nine of these cells (28%) exhibited maximum inhibition at the optimum orientation for the receptive field itself, but for 12 cells (38%) there was apparent 'release' from inhibition for surround gratings at or near the cell's optimum orientation and direction, leaving inhibition either maximal at angles flanking the optimum (9 cells) or broadly distributed over the rest of the orientation range (3 cells). This implies the existence of a subliminal facilitatory mechanism, tightly tuned at or near the cell's optimum orientation, extending outside the classical receptive field. For just two cells of 13 tested the preferred orientation for a central grating was clearly shifted towards the orientation of a surrounding grating tilted away from the cell's optimum. The contrast gain for central stimulation at the optimal orientation was measured with and without a surround pattern. For nine of 25 cells tested, surround stimulation at the cell's optimum orientation facilitated the response to a central grating of low contrast (< or =0.1) but inhibited that to a higher-contrast central stimulus: the contrast-response gain is reduced but the threshold contrast is actually decreased by surround stimulation. Hence the receptive field is effectively larger for low-contrast than for high-contrast stimuli. Inhibition from the periphery is usually greatest at or around the cell's optimum, while suppression within the receptive field has been shown to be largely non-selective for orientation. Inhibition by orientations flanking the optimum could serve to sharpen orientation selectivity in the presence of contextual stimuli and to enhance orientational contrast; and it may play a part in orientation contrast illusions.

Binocular rivalry: ambiguities resolved.

For over 100 years, binocular rivalry was seen as the result of competition between the two eyes, involving reciprocal suppression of retinal inputs. Now it emerges that rivalry reflects alternating perceptual interpretations that are represented in the firing patterns of cells in the temporal visual cortex.

Responses of neurons in primary and inferior temporal visual cortices to natural scenes.

The primary visual cortex (V1) is the first cortical area to receive visual input, and inferior temporal (IT) areas are among the last along the ventral visual pathway. We recorded, in area V1 of anaesthetized cats and area IT of awake macaque monkeys, responses of neurons to videos of natural scenes. Responses were analysed to test various hypotheses concerning the nature of neural coding in these two regions. A variety of spike-train statistics were measured including spike-count distributions, interspike interval distributions, coefficients of variation, power spectra, Fano factors and different sparseness measures. All statistics showed non-Poisson characteristics and several revealed self-similarity of the spike trains. Spike-count distributions were approximately exponential in both visual areas for eight different videos and for counting windows ranging from 50 ms to 5 seconds. The results suggest that the neurons maximize their information carrying capacity while maintaining a fixed long-term-average firing rate, or equivalently, minimize their average firing rate for a fixed information carrying capacity.

Visual motion processing in the anterior ectosylvian sulcus of the cat.

1. Neurons that are selectively sensitive to the direction of motion of elongated contours have been found in several cortical areas in many species. However, in the striate cortex of the cat and monkey, and the extrastriate posteromedial lateral suprasylvian visual area of the cat, such cells are generally component motion selective, signaling only the direction of movement orthogonal to the preferred orientation; a direction that is not necessarily the same as the motion of the entire pattern or texture of which the cell's preferred contour is part. The primate extrastriate middle temporal area is the only cortical region currently known to contain a substantial population of pattern-motion-selective cells that respond to the shared vector of motion of mixtures of contours. 2. From analyzing published data on the connectivity of the cat's cortex, we predicted that the anterior ectosylvian visual area (AEV), situated within the anterior ectosylvian sulcus, might be a higher-order motion processing area and thus likely to contain pattern-motion-selective neurons. This paper presents the results of a study on neuronal responses in AEV. 3. Ninety percent of AEV cells that responded strongly to drifting grating and/or plaid stimuli were directionally selective (directionality index > 0.5). For this group, the mean directionality index was 0.75. Moreover, 55% of these cells were unequivocally classified as pattern motion selective and only one neuron was classified as definitely component motion selective. Thus high-level pattern motion coding occurs in the cat extrastriate cortex and is not limited to the primate middle temporal area. 4. AEV contains a heterogeneous population of directionally selective cells. There was no clear relation between the degree of directional selectivity for plaids or gratings and the degree of selectivity for pattern motion or component motion. Nevertheless, 28% of the highly responsive cells were both more strongly modulated by plaids than gratings and more pattern motion selective than component motion selective. Such cells could correspond to a population of "selection units" signaling the salience of local motion information. 5. AEV lacks global retinotopic order but the preferred direction of motion of neurons (rather than axis of motion, as in the middle temporal area and the posteromedial lateral suprasylvian visual area) is mapped systematically across the cortex. Our data are compatible with AEV being a nonretinotopic, feature-mapped area in which cells representing similar parts of "motion space" are brought together on the cortical sheet.

The neural basis of suppression and amblyopia in strabismus.

The neurophysiological consequences of artificial strabismus in cats and monkeys have been studied for 30 years. However, until very recently no clear picture has emerged of neural deficits that might account for the powerful interocular suppression that strabismic humans experience, nor for the severe amblyopia that is often associated with convergent strabismus. Here we review the effects of squint on the integrative capacities of the primary visual cortex and propose a hypothesis about the relationship between suppression and amblyopia. Most neurons in the visual cortex of normal cats and monkeys can be excited through either eye and show strong facilitation during binocular stimulation with contours of similar orientation in the two eyes. But in strabismic animals, cortical neurons tend to fall into two populations of monocularly excitable cells and exhibit suppressive binocular interactions that share key properties with perceptual suppression in strabismic humans. Such interocular suppression, if prolonged and asymmetric (with input from the squinting eye habitually suppressed by that from the fixating eye), might lead to neural defects in the representation of the deviating eye and hence to amblyopia.

Functional architecture of area 17 in normal and monocularly deprived marmosets (Callithrix jacchus).

The organization of the primary visual cortex (VI) of the common marmoset (Callithrix jacchus) was studied both physiologically and by means of transneuronal labelling of geniculocortical afferents. We addressed the question whether monocular deprivation (MD) could stabilize segregation into ocular dominance (OD) columns, which are not seen in normal adult marmosets but are present in juvenile animals (Spatz, 1979, 1989). Properties of neurons in normal marmosets closely resembled those of other New-World and Old-World monkeys and orderly tangential progressions of preferred orientation were observed. However, in contrast to species that display well-defined OD columns, neurons of layer 4 in V1 of normal adult marmosets received balanced inputs from the two eyes. Early MD (even though followed by prolonged binocular experience into adulthood) resulted in a reduction of cell size in laminae of the lateral geniculate nucleus with input from the deprived eye and a dramatic overall shift in ocular dominance towards the nondeprived eye in the cortex. However, isolated clusters of cells dominated by the deprived eye were found in both layers 4 and 6. Injection of lectin-conjugated horseradish peroxidase (WGA-HRP) into the deprived eye revealed elongated patches of terminal label, about 350 microns wide, in flat-mounted sections through layer 4. Afferent segregation was sharper and more regular in the region of V1 representing parafoveal visual space than in that representing the fovea. Our findings support the notion that all Old-World and New-World monkeys possess the capacity for segregation of geniculocortical afferents into OD columns.

Interocular suppression in cat striate cortex is not orientation selective.

For the majority of neurones in cat striate cortex, the response to an optimal stimulus presented to one eye is suppressed when a stimulus of substantially different orientation is presented to the other eye. In order to determine the true orientational tuning of the underlying inhibitory interactions in the absence of binocular facilitation for matched stimuli, we tested how the response of such cells to an optimal grating in one eye is affected by gratings in the other eye of spatial frequencies too high or low to elicit an excitatory response through either eye: the vast majority of cells displayed suppression that was essentially independent of orientation. Our results indicate that interocular inhibition derives from cells representing all orientations, but is swamped by interocular facilitation for stimuli matched in orientation and spatial frequency.

Interocular suppression in the primary visual cortex: a possible neural basis of binocular rivalry.

In an attempt to demonstrate a physiological basis for the alternating suppression of perception when the two eyes view very different contours (binocular rivalry), we studied the responses of neurons in the lateral geniculate nucleus (LGN) and area 17 of cats for drifting gratings of different orientation, spatial frequency and contrast in the two eyes. Almost half of the LGN neurons studied exhibited modest inhibitory interocular interaction, but independent of interocular differences in orientation. Monocularly driven units in layer 4 of area 17 behaved similarly. However, for the majority of binocular cortical cells, the response to a grating of optimal orientation in one eye was suppressed by a grating of very different orientation shown to the other eye, over a wide range of spatial frequency and independent of relative spatial phase. This interocular suppression exhibits a remarkable non-linearity: a grating of non-preferred orientation in one eye causes significant interocular suppression only if the neuron is already responding to an appropriate stimulus in the other eye [Sengpiel and Blakemore (1994) Nature, 368, 847-850]. We propose that the switches in perceptual dominance during binocular rivalry depend on interocular interactions at the level of binocular neurons of the primary visual cortex, which might involve intracortical inhibition between adjacent ocular dominance columns. The spontaneous alternations in perceptual suppression that occur during prolonged viewing of rivalrous patterns remain to be explained, although significant variation in the strength of neuronal suppression in such conditions was occasionally seen.

Interocular suppression in the visual cortex of strabismic cats.

Strabismic humans usually experience powerful suppression of vision in the nonfixating eye. In an attempt to demonstrate physiological correlates of such suppression, we recorded from the primary visual cortex of cats with surgically induced squint and studied the responses of neurons to drifting gratings of different orientation, spatial frequency, and contrast in the two eyes. Only 1 of 50 apparently monocular cells showed any evidence of remaining, subliminal excitatory input from the "silent" eye when the two eyes were stimulated with gratings of similar orientation, and even among the small proportion of cells that remained binocularly driven, very few exhibited facilitation when stimulated binocularly. The majority of cells from both exotropes and esotropes, even those that could be independently driven through either eye, displayed nonspecific interocular suppression: stimulation of the nondominant eye with a drifting grating of any orientation depressed the response to an optimal grating being presented to the dominant eye. This phenomenon exhibited a gross nonlinearity in that it was dependent on the temporal sequence of stimulus presentation: stimulation of the nondominant eye caused significant suppression only if the neuron was already responding to an appropriate stimulus in the dominant eye, but not when onset of stimulation in the two eyes was simultaneous. Interocular suppression was always independent of the relative spatial phase of the two grating stimuli, and usually broadly tuned for the spatial frequency of the suppressive stimulus. Suppression may depend on inhibitory interaction between neighboring ocular dominance columns, combined with the loss of conventional disparity-selective binocular interactions for matched stimuli in the two eyes. The similarity of interocular suppression in strabismic cats and that caused by orthogonal gratings in the two eyes in normal cats (Sengpiel and Blakemore, 1994; Sengpiel et al., 1994) suggests that strabismic suppression and binocular rivalry depend on similar neural mechanisms.