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Biomedical subjects

T N Wiesel

Publications and source records attributed to T N Wiesel.

At least 19 recordsLinked to original sources

Receptive field dynamics in adult primary visual cortex.

The adult brain has a remarkable ability to adjust to changes in sensory input. Removal of afferent input to the somatosensory, auditory, motor or visual cortex results in a marked change of cortical topography. Changes in sensory activity can, over a period of months, alter receptive field size and cortical topography. Here we remove visual input by focal binocular retinal lesions and record from the same cortical sites before and within minutes after making the lesion and find immediate striking increases in receptive field size for cortical cells with receptive fields near the edge of the retinal scotoma. After a few months even the cortical areas that were initially silenced by the lesion recover visual activity, representing retinotopic loci surrounding the lesion. At the level of the lateral geniculate nucleus, which provides the visual input to the striate cortex, a large silent region remains. Furthermore, anatomical studies show that the spread of geniculocortical afferents is insufficient to account for the cortical recovery. The results indicate that the topographic reorganization within the cortex was largely due to synaptic changes intrinsic to the cortex, perhaps through the plexus of long-range horizontal connections.

Afferent Pathways

Targets of horizontal connections in macaque primary visual cortex.

Pyramidal neurons within the cerebral cortex are known to make long-range horizontal connections via an extensive axonal collateral system. The synaptic characteristics and specificities of these connections were studied at the ultrastructural level. Two superficial layer pyramidal cells in the primate striate cortex were labeled by intracellular injections with horseradish peroxidase (HRP) and their axon terminals were subsequently examined with the technique of electron microscopic (EM) serial reconstruction. At the light microscopic level both cells showed the characteristic pattern of widespread, clustered axon collaterals. We examined collateral clusters located near the dendritic field (proximal) and approximately 0.5 mm away (distal). The synapses were of the asymmetric/round vesicle variety (type I), and were therefore presumably excitatory. Three-quarters of the postsynaptic targets were the dendritic spines of other pyramidal cells. A few of the axodendritic synapses were with the shafts of pyramidal cells, bringing the proportion of pyramidal cell targets to 80%. The remaining labeled endings were made with the dendritic shafts of smooth stellate cells, which are presumed to be (GABA)ergic inhibitory cells. On the basis of serial reconstruction of a few of these cells and their dendrites, a likely candidate for one target inhibitory cell is the small-medium basket cell. Taken together, this pattern of outputs suggests a mixture of postsynaptic effects mediated by consequence the horizontal connections may well be the substrate for the variety of influences observed between the receptive field center and its surround.

Animals

Immunolabelling by a newt retinal pigment epithelium antibody during retinal development and regeneration.

The binding of RPE-1, a mouse monoclonal antibody selective for newt retinal pigment epithelium, was followed in eyes undergoing embryonic development and retinal regeneration. Using the indirect immunofluorescence technique on frozen sections, we observed bright and continuous labelling exclusively in the retinal pigment epithelium (RPE) of normal adult newts, but labelling became diminished near the ora serrata region and stopped abruptly at the ciliary margin. During development, labelling was not detected in the retinal pigment epithelium (RPE) until the formation of photoreceptor outer segments and was not observed in any other ocular tissue. There was no correlation between the appearance of pigment in retinal pigment epithelial cells and their labelling with the RPE-1 antibody. Furthermore, albino salamander embryos showed the same pattern of labelling with RPE-1 as that seen in age-matched pigmented animals. During retinal regeneration, RPE cells were labelled less intensely, but heavy labelling was observed in the newly formed retinal cells. With time, labelling in regenerated retina receded, so that by the end of regeneration, labelling by RPE-1 was once more restricted to the RPE cells. The identification of RPE-1 as a marker for postmitotic retinal neurons about to undergo differentiation provides a promising approach for further studies of regeneration with the help of molecular tools.

Albinism

Neural control of eye growth and experimental myopia in primates.

Macaque monkeys become myopic when raised with fused lids to expose the retina to formless shadows during the period of postnatal eye development. The effect of the abnormal visual input is an excessive expansion of the posterior segment of the eye, a process that seems to be controlled by the nervous system. The mechanism by which the nervous system influences eye growth appears to be different in the stumptailed macaque (Macaca arctoides) and the rhesus macaque (M. mulatta). Lid-fused arctoides monkeys do not develop myopia when the ciliary muscle is paralysed or the optic nerve is cut, suggesting that the abnormal growth is caused by excessive accommodation. In contrast, paralysis of the ciliary muscle or optic nerve section does not prevent the development of myopia in the rhesus macaque, suggesting that in this species the axial growth is controlled by the retina. In both species neonatal lid fusion causes a marked increase in retinal vasoactive intestinal polypeptide (VIP). VIP is contained in a single type of amacrine cell whose dendrites spread in the middle of the inner plexiform layer. It remains to be determined whether the increase in the level of VIP is related to the abnormal axial elongation caused by lid fusion. At present we are also exploring the effects of accommodation on the growth of the eye by training juvenile arctoides monkeys to work on complex visual discrimination paradigms. Preliminary results show that performing a visual task at close range may influence the axial length and refraction in this macaque species.

Accommodation, Ocular

The influence of contextual stimuli on the orientation selectivity of cells in primary visual cortex of the cat.

Perception of a visual attribute, such as orientation, is strongly dependent on the context within which a feature is presented, such as that seen in the tilt illusion. The possibility that the neurophysiological basis for this phenomenon may be manifest at the level of cells in striate cortex is suggested by anatomical and physiological observations of orientation dependent long range horizontal connections which relate disparate points in the visual field. This study explores the dependency of the functional properties of single cells on visual context. We observed several influences of the visual field area surrounding cells' receptive field on the properties of the receptive field center: inhibition or facilitation dependent on the orientation of the surround, shifts in orientation preference and changes in the bandwidth of orientation tuning. To relate these changes to perceptual changes in orientation we modeled a neuronal ensemble encoding orientation. Our results show that the filter characteristics of striate cortical cells are not necessarily fixed, but can be dynamic, changing according to context.

Animals

Lateral interactions in visual cortex.

The findings presented in these studies have brought out different ideas concerning the mechanisms of processing in primary visual cortex than were held at the outset. Rather than thinking of receptive fields as being restricted in their extent, with the process of integration of the components of an image occurring at a much later stage along the visual pathway, we have shown that the integrative process is a progressive one, beginning in the primary visual cortex (or perhaps even earlier) and building up in a cascading series of converging and diverging connections. Rather than thinking of the filter characteristics of a cell as being fixed, it is apparent that they are dynamic and can be modified by the context in which features are presented. Finally, rather than a cortex with a functional architecture that is fixed after a critical period ending in infancy, we find that perturbing the system can lead to long-term topographical reorganization. Other examples of contextual interactions have been demonstrated in the submodalities of motion, where a cell's directional selectivity is modulated by the presence of movement in the surround (Allman et al. 1985; Tanaka et al. 1986; Gulyas et al. 1987; Orban et al. 1987). In the domain of color, the phenomenon of color constancy, reported for cells in visual area V4 (Zeki 1983), also requires lateral interactions in visual space, comparing the wavelength distribution of light coming from surfaces in different parts of the visual field. The influences presented in these studies, as in our own work in the domain of orientation, are modulatory. The long-term changes in cortical topography following removal of somatosensory input (Merzenich et al. 1984, 1988) or by retinal lesions suggest that with the appropriate manipulations the lateral interactions can be enhanced to the point of activating the postsynaptic cells. Although retinal lesions clearly represent an abnormal disruption of sensory input, they may nevertheless be representative of long-term reorganizations of neural networks occurring under normal circumstances, such as those required for memory.

Animals

Pharmacological analysis of cortical circuitry.

The cortical circuitry of the visual cortex has been worked out in great detail. Anatomical investigations reveal stereotyped connections within cortical columns and specific long-range connections between distant columns. Pharmacological techniques for blocking the activity in individual cortical layers or columns allow the microdissection of the cortical circuit. These studies could relate specific functional roles to particular cortical connections.

Animals

Local circuits and ocular dominance columns in monkey striate cortex.

The relationships between ocular dominance columns and intrinsic cortical circuitry were examined in brain slices prepared from the striate cortex of macaques. Ocular dominance columns in layer 4C beta were visualized in vitro following anterograde transport of rhodamine injected into the lateral geniculate nucleus in vivo. The axonal and dendritic arborizations of individual layer 4C beta cells were revealed by intracellular fluorescent dye injections. Both qualitative observations and quantitative analysis showed that the dendrites of cells close to borders remained preferentially, although not absolutely, in the "home" column (the column containing the cell body). Thus, the segregated pattern of afferent input appears to have considerable influence on the pattern of dendritic arbors. Similarly, while axon collaterals within layer 4C beta could cross into the adjacent column, their limited lateral spread produced arbors that remained primarily within the home column. The terminal arbors of collaterals that travelled from layer 4C beta to layer 3 had a larger lateral spread, and the termination pattern appeared to be independent of column borders. Thus, our observations indicate that, while the course of many layer 4C beta dendrites appears to be guided by columnar boundaries as defined by geniculate afferents, there exist morphological substrates for intercolumnar interactions even between 4C beta cells. Intercolumnar interactions are seen more commonly in layer 3, however, where larger, denser axon arbors originating from 4C beta cells can freely cross ocular dominance column boundaries.

Animals

Columnar specificity of intrinsic horizontal and corticocortical connections in cat visual cortex.

A prominent and stereotypical feature of cortical circuitry in the striate cortex is a plexus of long-range horizontal connections, running for 6-8 mm parallel to the cortical surface, which has a clustered distribution. This is seen for both intrinsic cortical connections within a particular cortical area and the convergent and divergent connections running between area 17 and other cortical areas. To determine if these connections are related to the columnar functional architecture of cortex, we combined labeling of the horizontal connections by retrograde transport of rhodamine-filled latex microspheres (beads) and labeling of the orientation columns by 2-deoxyglucose autoradiography. We first mapped the distribution of orientation columns in a small region of area 17 or 18, then made a small injection of beads into the center of an orientation column of defined specificity, and after allowing for retrograde transport, labeled vertical orientation columns with the 2-deoxyglucose technique. The retrogradely labeled cells were confined to regions of orientation specificity similar to that of the injection site, indicating that the horizontal connections run between columns of similar orientation specificity. This relationship was demonstrated for both the intrinsic horizontal and corticocortical connections. The extent of the horizontal connections, which allows single cells to integrate information over larger parts of the visual field than that covered by their receptive fields, and the functional specificity of the connections, suggests possible roles for these connections in visual processing.

Animals

Increase in retinal vasoactive intestinal polypeptide after eyelid fusion in primates.

Lids were fused in six neonatal and one adult macaque monkey (Macaca mulatta and Macaca arctoides) and were kept fused for 1 to 18.5 months. The juvenile macaques, but not the adult one, developed myopia due to excessive elongation of the eye. In all animals, the immunohistochemical reactivity of the retina for vasoactive intestinal polypeptide (VIP) was much higher in the closed than in the open eyes. The neuropeptide was localized to the perikaryon and dendrites of amacrine cells. No difference was observed in substance P immunoreactivity between open and closed eyes, suggesting that the observed effect is selective. The change in VIP immunoreactivity could be the result of an increase in peptide synthesis, a decrease in peptide release, or a combination of the two. These results indicate that VIP may play a part in the regulation of postnatal ocular growth.

Animals

Morphology and intracortical projections of functionally characterised neurones in the cat visual cortex.

The neuronal structure and connectivity underlying receptive field organisation of cells in the cat visual cortex have been investigated. Intracellular recordings were made using a micropipette filled with a histochemical marker, which was injected into the cells after their receptive fields had been characterised. This allowed visualisation of the dendritic and axonal arborisations of functionally identified neurones.

Afferent Pathways

Increase in axial length of the macaque monkey eye after corneal opacification.

The cornea of one eye was opacified in two young macaque monkeys by multiple stromal injections of a suspension of polystyrene particles (latex). Ultrasound measurements showed that the eye with opaque cornea grew at a faster rate, so that after 1 year it was more than 1 mm longer than the normal eye. This difference in axial length was due to elongation of the posterior segment, since lens thickness, depth of anterior chamber, and corneal curvature were identical in both eyes. At histological examination, no pathological changes were observed in the anterior segment of the latex-injected eye except for a scant vascularization of the corneal opacity. The result of this experiment demonstrates that opacification of the corneal has effects on axial length similar to, although less marked than, those on lid fusion and therefore supports our previous conclusion that the myopia caused by lid fusion is triggered by the abnormal visual impact and involves central visual pathways.

Animals

Effect of dark-rearing on experimental myopia in monkeys.

When lids are surgically fused in rhesus monkeys before eye growth is completed, a high degree of myopia develops, which is caused by an elongation of the eye globe. The present study shows that in monkeys raised in the dark after monocular lid fusion, refraction and axial length were normal in both the closed and the open eye. Myopia, however, readily developed and the eye elongated when a monkey raised in the dark was transferred to illuminated quarters. These findings indicate that visual stimulation through the translucent lids was necessary for the development of this experimental ametropia.

Animals