Early postnatal development of functional ocular dominance columns in cat primary visual cortex

During postnatal development of the visual cortex the thalamocortical afferents serving the two eyes segregate into alternating patches called ocular dominance (OD) columns. Interested in the dynamics of this segregation process we studied the appearance of functional OD columns in the primary visual cortex of normally raised and strabismic kittens aged 2-6 weeks using 2-deoxyglucose labelling in awake animals. In both experimental groups, OD columns covering the entire area 17 and spanning all cortical laminae are first visible at 3 weeks and appear already adult-like at 4 weeks, much earlier than thought on the basis of previous anatomical studies. We hypothesize that a small and anatomically undetectable imbalance between the afferents from the two eyes is amplified by intracortical interactions so that their activity patterns become different and may guide the segregation process of the afferents in cortical layer IV.     

Analysis of monocular optokinetic nystagmus in normal and visually deprived kittens

The asymmetry of monocular OKN was assessed in normal, monocularly deprived (non-deprived eye) and strabismic cats. No significant differences were observed between the responses of these 3 groups. In young kittens, the gain of OKN for nasalward stimulus was larger than that for temporalward. This asymmetry declined to a low residual level by about one year of age. Neurophysiological recordings indicated that the symmetry of OKN is not related to cortical binocularity.     

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.     

Development of the dorsal lateral geniculate nucleus in normal and visually deprived cats

Although much is known about the cell size changes that take place in the cat dorsal lateral geniculate nucleus as a result of visual deprivation, very little is known about the time course of either of these changes or the changes that occur during normal development. In addition, all previous studies of lateral geniculate nucleus cell size have been confined to the dorsal laminae A and A1 since the more ventral “C” laminae are impossible to identify in normal Nissl stained material. However, it is possible to extend the cell measurement data to laminae C, C1, and C2 by using autoradiographic techniques. Cross-sectional area measurements of dorsal lateral geniculate nucleus cells were made in 47 normally reared kittens and 45 monocularly deprived kittens. All of the normal kittens and 39 of the 45 deprived kittens were studied during the first 70 days of postnatal life. Six deprived cats used to study the deprivatin induced changes in cell size in the “C” laminae were allowed to survive for longer periods. In normal kittens, lateral geniculate nucleus cells grow rapidly during the first four weeks of life. Cells in the deprived layers also grow rapidly during this time, however, at the end of the first month their growth stops and a slow shrinkage takes place over the next several weeks. In the ‘C’ laminae of deprived cats significant changes in cell size are confined to layer C. Although many of the deprived cats show greater deprivation induced changes in cell size in the binocular segment of the lateral geniculate nucleus than in the monocular segment, other cats show approximately equal changes in cell size in the two regions. In addition, some cats exhibit little, if any, deprivation induced change in lamina A cell size but do show quite severe cell shrinkage in lamina A1.     

Direct mapping of ocular dominance columns in human primary visual cortex

Functional magnetic resonance imaging at 2.0T was employed to identify columnar structures in human visual cortex. Sagittal sections (4 mm thickness) covering the calcarine cortex were acquired with use of a multiecho low flip angle gradient-echo sequence at 4.0 s temporal resolution and 0.25 x 0.25 mm2 spatial resolution. Extending earlier attempts based on a differential paradigm contrasting left vs right eye stimulation, this work presents the first direct mapping of human ocular dominance columns by measuring separate activation maps with left and right eye stimulation. The resulting individual maps reveal patterns of ocular dominance as spots or bands of altered activity in calcarine cortex. Their superposition shows only little spatial overlap of eye-specific encoding which strongly supports the genuineness of these functional units.     

Penicillin-induced epileptiform activity does not prevent ocular dominance shifts in monocularly deprived kittens

Epileptiform activity was induced in the visual cortex with penicillin to test whether it would prevent the ocular dominance shift that normally occurs in monocularly deprived kittens. The eyelids of one eye of 5-week-old kittens were sutured shut for several days. During this period, whenever the kittens were in the light, aqueous penicillin in artificial cerebrospinal fluid (CSF) or just CSF was applied in a cylinder mounted over the visual cortex. Electroencephalograms monitored during the period of deprivation indicated nearly continuous interictal spiking in the visual cortex. Extracellular recordings were made of cells in the region directly under the position of the cylinder. 14C-labeled 2-deoxyglucose autoradiography in a control kitten showed that this area had considerably increased metabolism during epileptiform activity. The majority of cortical cells were dominated by the non-deprived eye in both epileptic and control kittens, with no noticeable difference between them. These preliminary observations indicate that the disruption of cortical activity that occurs during interictal epileptiform activity does not prevent the ocular dominance shift in monocularly deprived kittens.     

Cell-specific expression of type II calcium/calmodulin-dependent protein kinase isoforms and glutamate receptors in normal and visually deprived lateral geniculate nucleus of monkeys

In situ hybridization histochemistry and immunocytochemistry were used to map distributions of cells expressing mRNAs encoding α, β, γ, and δ isoforms of type II calcium/calmodulin-dependent protein kinase (CaMKII), α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)/kainate receptor subunits, (GluR1–7), and N-methyl-D-aspartate (NMDA) receptor subunits, NR1 and NR2A-D, or stained by subunit-specific immunocytochemistry in the dorsal lateral geniculate nuclei of macaque monkeys. Relationships of specific isoforms with particular glutamate receptor types may be important elements in neural plasticity. CaMKII-α is expressed only by neurons in the S laminae and interlaminar plexuses of the dorsal lateral geniculate nucleus, but may form part of a more widely distributed matrix of similar cells extending from the geniculate into adjacent nuclei. CaMKII-β, -γ, and -δ isoforms are expressed by all neurons in principal and S laminae and interlaminar plexuses. In principal laminae, they are down-regulated by monocular deprivation lasting 8–21 days. All glutamate receptor subunits are expressed by neurons in principal and S laminae and interlaminar plexuses. The AMPA/kainate subunits, GluR1, 2, 5, and 7, are expressed at low levels, although GluR1 immunostaining appears selectively to stain interneurons. GluR3 is expressed at weak, GluR 6 at moderate and GluR 4 at high levels. NMDA subunits, NR1 and NR2A, B, and D, are expressed at moderate to low levels. GluR4, GluR6 and NMDA subunits are down-regulated by visual deprivation. CaMKII-α expression is unique in comparison with other CaMKII isoforms which may, therefore, have more generalized roles in cell function. The results demonstrate that all of the isoforms are associated with NMDA receptors and with AMPA receptors enriched with GluR4 subunits, which implies high calcium permeability and rapid gating. J. Comp. Neurol. 390:278–296, 1998. © 1998 Wiley-Liss, Inc.     

The development of the somatosensory representation in the superior colliculus of visually deprived mice.

Mice were enucleated bilaterally at birth in order to investigate whether early visual deprivation had any influence on the development of the somatosensory representation in the superior colliculus (SC). Single unit recordings were performed during the 2nd, 3rd, 5th and 8th postnatal week in both normal and enucleated mice. It was found that, in visually deprived mice, there was a dramatic increase of the SC somatosensory units starting from the 3rd postnatal week, as occurs in normal mice. During the 5th and 8th postnatal week, this increase was larger than in normal mice, mainly due to the invasion of the somatosensory input into the superficial layers. In visually deprived mice, both the orientation of the somatosensory map and the magnification of some body parts, such as the upper vibrissae, did not show any difference with respect to normal mice. These results indicate the involvement of both vision-dependent and independent mechanisms in the formation of the SC somatosensory representation. In fact, whereas the segregation of the somatosensory afferents in the deep layers depended on the presence of visual input, the postnatal emergence and the topographic arrangement of the somatosensory map resulted to be independent of vision.     

Topographic shear and the relation of ocular dominance columns to orientation columns in primate and cat visual cortex

Shear has been known to exist for many years in the topographic structure of the primary visual cortex, but has received little attention in the modeling literature. Although the topographic map of V1 is largely conformal (i.e. zero shear), several groups have observed topographic shear in the region of the V1/V2 border. Furthermore, shear has also been revealed by anisotropy of cortical magnification factor within a single ocular dominance column. In the present paper, we make a functional hypothesis: the major axis of the topographic shear tensor provides cortical neurons with a preferred direction of orientation tuning. We demonstrate that isotropic neuronal summation of a sheared topographic map, in the presence of additional random shear, can provide the major features of cortical functional architecture with the ocular dominance column system acting as the principal source of the shear tensor. The major principal axis of the shear tensor determines the direction and its eigenvalues the relative strength of cortical orientation preference. This hypothesis is then shown to be qualitatively consistent with a variety of experimental results on cat and monkey orientation column properties obtained from optical recording and from other anatomical and physiological techniques. In addition, we show that a recent result of Das and Gilbert (Das, A., & Gilbert, C. D., 1997. Distortions of visuotopic map match orientation singularities in primary visual cortex. Nature, 387, 594–598) is consistent with an infinite set of parameterized solutions for the cortical map. We exploit this freedom to choose a particular instance of the Das–Gilbert solution set which is consistent with the full range of local spatial structure in V1. These results suggest that further relationships between ocular dominance columns, orientation columns, and local topography may be revealed by experimental testing.     

Loss of ocular dominance columns with maturity in the monkey, Callithrix jacchus

Previous studies have shown that adult marmosets lack ocular dominance columns (ODC) in area 17, but that ODCs can be demonstrated upon visual deprivation. The present results, obtained by transneuronal transport of WGA-HRP, indicate that ODCs normally develop in juvenile marmosets but disappear before the animal reaches maturity. The findings suggest that formation of ODCs during ontogenesis, and their persistence through adulthood, are different developmental processes depending on different mechanisms.     

Distributions of synaptic vesicle proteins and GAD65 in deprived and nondeprived ocular dominance columns in layer IV of kitten primary visual cortex are unaffected by monocular deprivation

Two days of monocular deprivation (MD) of kittens during a critical period of development is known to produce a loss of visual responses in the primary visual cortex to stimulation of the nondeprived eye, and 7 days of deprivation results in retraction of axon branches and loss of presynaptic sites from deprived-eye geniculocortical arbors. The rapid loss of responsiveness to deprived-eye visual stimulation could be due to a decrease in intracortical excitatory input to deprived-eye ocular dominance columns (ODCs) relative to nondeprived-eye columns. Alternatively, deprived-eye visual responses could be suppressed by an increase in intracortical inhibition in deprived columns relative to nondeprived columns. We tested these hypotheses in critical period kittens by labeling ODCs in layer IV of primary visual cortex with injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into lamina A of the lateral geniculate nucleus (LGN). After either 2 or 7 days of MD, densities of intracortical excitatory presynaptic sites within deprived relative to nondeprived ODCs were estimated by measuring synaptic vesicle protein (SVP) immunoreactivity (IR). Because most of the synapses within layer IV of primary visual cortex are excitatory inputs from other cortical neurons, levels of SVP-IR provide an estimate of the amount of intracortical excitatory input. We also measured levels of immunoreactivity of the inhibitory presynaptic terminal marker glutamic acid decarboxylase (GAD)65 in deprived relative to nondeprived ODCs. Monocular deprivation (either 2 or 7 days) had no effect on the distributions of either SVP- or GAD65-IR in deprived and nondeprived columns. Therefore, the rapid loss of deprived-eye visual responsiveness following MD is due neither to a decrease in intracortical excitatory presynaptic sites nor to an increase in intracortical inhibitory presynaptic sites in layer IV of deprived-eye ODCs relative to nondeprived columns.     

The pattern of ocular dominance columns in macaque visual cortex revealed by a reduced silver stain

A pattern of alternative dark and pale bands was observed in the straite cortex of the macaque monkey. The bands, which ran parallel to the surface, were seen in tangential sections stained with a reduced silver method for normal fibers and were most clear in layer 4C α, immediately deep to the line of Gennari. The dark bands were about 300 μ wide and showed blind endings and bifurcations. The light bands were about 50 μ wide and did not branch or terminate within area 17. Because the dark bands were similar in width to the bands of terminal degeneration which have been shown to result from single-layer lesions of the lateral geniculate body, it seemed possible that they corresponded to ocular dominance columns. To test this idea, the boundaries of ocular dominance columns were marked in a physiological experiment: tangential electrode penetrations were made in an anesthetized monkey and, as the electrode was advanced horizontally in the fourth layer, the eye preference of single units and of the background activity was monitored. Small electrolytic lesions were placed at the points where a change in eye preference occurred. The brain was subsequently fixed, sectioned tangentially and stained with the silver method. All the lesions — a total of 12 — fell directly on the pale bands. Moreover, the electrode had not passed over any pale bands without a lesion being placed. It was concluded that the dark bands do correspond to single ocular dominance columns and the pale bands to the boundaries between columns. The banding appearance is due to a greater density of tangential fibers within columns than at the borders of columns. These tangential fibers are in part the preterminal arborizations of geniculocortical axons, since some of them have been shown to degenerate after geniculate lesion. The ocular dominance columns were mapped for most of the striate cortex, using serial tengential sections stained with the silver method. The overall pattern was similar in several monkeys, though the details of the branching arrangements vaired from animal to animal. The columns met the 17–18 border at rigtht angles. On the outer surface of the hemisphere the columns converged from the 17–18 border, turned medially with repeated fusions of columns, and streamed over the lip of the calcarine fissure. In the roof of the fissure they met a second system of columns oriented parasagittally. In terms of the visual field, the columns ran roughly horizontally for the central 10° of the field, and circumferentially beyond that. The columns were not mapped in the stem of the fissure, the area corresponding to the far periphery of the field. The constancy of column width across the cortex probably allows a functional matching between ocular-dominance and orientation columns.     

Emergence of ocular dominance columns in cat visual cortex by 2 weeks of age

Previous anatomic studies of the geniculocortical projection showed that ocular dominance columns emerge by 3 weeks of age in cat visual cortex, but recent optical imaging experiments have revealed a pattern of physiologic eye dominance by the end of the second week of life. We used two methods to search for an anatomic correlate of this early functional ocular dominance pattern. First, retrograde labeling of lateral geniculate nucleus (LGN) inputs to areas of cortex preferentially activated by one eye showed that the geniculocortical projection was already partially segregated by eye at postnatal day 14 (P14). Second, transneuronal label of geniculocortical afferents in flattened sections of cortex after a tracer injection into one eye showed a periodic pattern at P14 but not at P7. In the classic model for the development of ocular dominance columns, initially overlapping geniculocortical afferents segregate by means of an activity-dependent competitive process. Our data are consistent with this model but suggest that ocular dominance column formation begins between P7 and P14, approximately a week earlier than previously believed. The functional and anatomic data also reveal an early developmental bias toward contralateral eye afferents. This initial developmental bias is not consistent with a strictly Hebbian model for geniculocortical afferent segregation. The emergence of ocular dominance columns before the onset of the critical period for visual deprivation also suggests that the mechanisms for ocular dominance column formation may be partially distinct from those mediating plasticity later in life.     

Ocular dominance columns and retinal projections in New World spider monkeys (Ateles ater)

Retinal projections and the degree of ocular segregation in the striate cortex were examined by transneuronal autoradiography following unilateral intraocular injections of 3H-proline in a New World primate, the spider monkey (Ateles ater). The results show that, within the lateral geniculate nucleus (LGN), retinal fibers terminate in six principal layers and within the interlaminar spaces adjacent to the magnocellular layers, as well as the S layers ventral to the magnocellular layers. Projections to the superior colliculus, both ipsilateral and contralateral to the injected eye, were patchy and restricted to the superficial gray layer. Our main result shows that, in the striate cortex, LGN projections terminate in well-defined ocular dominance columns in layer IV. Labelled columns were most clearly delimited in layer IVb, where they averaged 373 + 42 micron in width in both the ipsilateral and contralateral hemispheres, slightly smaller than those reported originally from electrophysiological studies of striate cortex in spider monkeys (Hubel and Wiesel, '68). Unlabelled intercolumns were significantly narrower than labelled columns, which suggests that there may be overlap between input from the two eyes between columns. Quantitative measures showed above-background label also in cortical layers IIIb, V, and VI. Our results support the idea that among primates, ocular dominance columns are not limited to Old World species. At the same time, it is apparent that spider monkeys are exceptional among New World primates in having sharply delimited columns. The functional significance of the variation in the degree of ocular segregation in the cortex and its relation to primate evolution are discussed.     

Improved auditory spatial acuity in visually deprived ferrets

We have examined the effects on auditory spatial acuity in the horizontal plane of depriving ferrets of patterned visual cues by binocular eyelid suture in infancy or for a comparable period in adulthood. Minimum audible angles (MAAs) were measured for 500-, 100- and 40-ms broadband noise bursts at the midline and at 45 degrees to one side. A logistic regression analysis revealed no consistent difference between the midline MAAs of normal and infant lid-sutured ferrets. However, the lateral field MAAs of the infant-deprived group were significantly smaller and showed less inter-subject variability than those of normal-sighted ferrets. The animals deprived in adulthood were tested in the lateral field only, firstly 6 months after binocular eyelid suture and again after a further 10 months. For the first test, the MAAs achieved by these animals with 500- and 100-ms noise bursts were significantly smaller than the normal values and no different from those of the infant-deprived group. A significant improvement in performance at the two shortest stimulus durations (100 and 40 ms) was observed when the adult-deprived animals were re-tested. Their second-test MAAs did not differ from those of the infant-deprived group at any of the three stimulus durations used, and both groups achieved significantly better scores than the normal-sighted control animals. These results show that prolonged visual deprivation in both juvenile and adult ferrets can lead to a significant improvement in auditory spatial acuity in the lateral sound field. This is consistent with reports that congenitally blind humans can localize peripheral sounds more accurately than normal controls.