Evidence That the Lateral Geniculate Nucleus Regulates the Normal Development of Visual Corticocortical Projections in the Cat

The aim of this work was to examine the influence of subcortical afferents on the development of corticocortical projections in the cat's visual cortex. In the adult, corticocortical axons project with precision to link retinotopically corresponding points in visual areas 17 and 18. In the newborn kitten, an excess of corticocortical connections is generated, leading to a degree of imprecision in the early pathways. During the first postnatal month, the loss of some of these early connections lowers their densities and increases the accuracy with which they project. These processes occur in an environment already influenced by afferents from the lateral geniculate nucleus and we tested the extent to which these existing inputs are required for corticocortical development. We lesioned the lateral geniculate nucleus with ibotenic acid in newborn kittens and studied connections from area 17 to area 18, and vice versa, after 1 month. In lesioned kittens, there were fewer corticocortical projections than normal in these reciprocal pathways and those that were present retained an immature, widespread pattern of projection. These results suggest that geniculate afferents are crucial for generating sufficient numbers of corticocortical projections and for creating the precision in their mapping.     

The Role of Horizontal Connections in Generating Long Receptive Fields in the Cat Visual Cortex

The cells in the primary visual cortex possess numerous functional properties that are more complex and varied than those seen in the cortical input. These properties result from the network of intrinsic cortical connections running across the cortical layers and between cortical columns. In the current study we relate the long receptive fields that are characteristic of layer 6 cells to the input that these cells receive from layer 5. The axons of layer 5 pyramidal cells project over long distances within layer 6, enabling layer 6 cells to collect input from regions of cortex representing large parts of the visual field. When layer 5 was locally inactivated by injection of the inhibitory transmitter GABA, layer 6 cells lost sensitivity over the portion of their receptive fields corresponding to the inactivated region of layer 5. This suggests that the extensive convergence in the projection from layer 5 to layer 6 is responsible for generating the long receptive fields characteristic of the layer 6 cells.     

Formation of Specific Efferent Connections in Organotypic Slice Cultures from Rat Visual Cortex Cocultured with Lateral Geniculate Nucleus and Superior Colliculus

Cells in the cerebral cortex project to many distant regions in the brain. Each cortical target receives input from a specific population of cells which have a characteristic morphology and which are located in a distinct cortical layer. In an attempt to learn about the mechanisms by which this stereotypic output pattern is generated during development, we have studied the formation of cortical projections in an in vitro system. Slices from developing rat visual cortex were cocultured with slices from the superior colliculus, the major target of cells in layer 5, and the lateral geniculate nucleus, the major target of cells in layer 6. Cortical neurons which established connections with tectal and thalamic explants were retrogradely labelled with fluorescent dyes. It was found that, in vitro , different populations of neurons project to these two targets, and that the laminar position and cellular morphology of the projecting cells were similar to their in vivo counterparts. These specific connections were established when the target explants were placed either next to the white matter or next to the pial side of cortical slice cultures. The axons of cells projecting to ectopic positioned explants reoriented their trajectories and grew through the cortical grey matter directly towards their targets. Thus subcortical targets exert an orienting effect specifically on their innervating cells and attract growing axons of the appropriate cells at a distance. These results suggest that different targets release different molecules that act selectively on specific populations of neurons. Therefore, chemotropic guidance is likely to play a significant role in the development of specific connections between cortical neurons and their target areas.     

The Topography of Tangential Inhibitory Connections in the Postnatally Developing and Mature Striate Cortex of the Cat

Clustered intrinsic connections in the striate cortex of kittens originate from an unclustered, diffusely organized pattern prevailing during the first postnatal week. In order to study the participation of inhibitory neurons in this reorganization of the connections, we determined the topography of the inhibitory tangential connections in the striate cortex of cats ranging in age between 7 and 330 days by combining retrograde transport of fluorescent microspheres with GABA immunohistochemistry. After small intracortical injections of tracer, neurons containing either microspheres only (non-GABAergic neurons) or GABA-like immunoreactivity in addition to microspheres (GABAergic neurons) are labelled at various horizontal distances from the injection. At the end of the first postnatal week, both GABAergic and non-GABAergic neurons are distributed in the horizontal plane in an unclustered fashion. During the second postnatal week, the tangential connections rearrange rapidly to form clusters. The tendency of the cells to form clusters is much weaker, however, in GABAergic than in non-GABAergic neurons. In regions >500 μm distant from the centre of injection ～90% of the non-GABAergic neurons (range 87.5-92.6%) but only 63% (range 57.1 – 72.3%) of the GABAergic neurons reside within the clusters formed by the non-GABAergic neurons. These proportions do not change systematically with age. In the regions outside the non-GABAergic clusters, GABAergic neurons appear to be evenly distributed and not to aggregate in clusters. From postnatal day 7 forward GABAergic neurons largely retain their overall distribution and density in the horizontal plane. When considering all cortical layers (including the superficial white matter) the lateral spread of the GABAergic neurons is more restricted than that of the non-GABAergic neurons. Systematic changes in the lateral spread of inhibitory connections according to postnatal age were not observed. We conclude that, like the non-GABAergic neurons, the GABAergic neurons have attained an adult-like topography in the horizontal plane by about the end of the second postnatal week. From that time until adulthood they display much weaker clustering, a higher relative occurrence of short axon collaterals and a more restricted lateral distribution than do the excitatory neurons.     

Optical Imaging of the Layout of Functional Domains in Area 17 and Across the Area 17/18 Border in Cat Visual Cortex

Optical imaging based on intrinsic signals was used to investigate the functional architecture of cat area 17 and the border between areas 17 and 18. The visual stimuli were gratings of different spatial frequencies moving at different angles, in different directions and with different speeds. In area 17 the iso-orientation domains were usually organized in patches rather than as elongated bands. Patches with different orientation preferences were arranged radially forming 'pinwheels' around 'orientation centres'. The pinwheel density was ∼1.7-fold higher than in area 18. To explore clustering according to direction of motion, stimuli having the same orientation but moving in opposite directions were used. These two stimuli yielded very similar activity maps giving no indication of robust directionality clustering. Using near infrared light we were able to simultaneously image ocular-dominance and iso-orientation domains. A quantitative assessment of the relative strengths of the two subsystems showed that in upper cortical layers clustering according to orientation preference was three-fold stronger than clustering according to ocular dominance. The functional organization of spatial frequency was also examined. When we compared the activated regions by stimuli having different spatial frequency and moving at different velocities we observed that neurons were clustered also in these respects. We also investigated the functional architecture at the area 17/18 border and found that orientation maps at both sides of the border were not independent of each other. The map of area 17 smoothly blended into that of area 18. Similarly, the preferred spatial frequency of the neurons changed gradually over a distance of ∼0.8 mm at the region of the area 17/18 border.     

Specificity in the Development of Vertical Connections in Cat Striate Cortex

The main efferent axons of pyramidal cells in layer 2/3 in the adult cat striate cortex make collateral connections specifically within layer 2/3 and layer 5 and avoid the intervening layer 4. Intracellular dye injections in vitro were used to determine how, during early postnatal development, this precise pattern of laminar connections was achieved. These investigations revealed that the pattern of collateral outgrowth was specific from the very earliest time that axons began sprouting collaterals. During the first postnatal week, sprouts were seen exclusively within layers 2/3 and 5; no evidence for a transient connection to layer 4 was observed. Furthermore, collaterals emerged simultaneously within layers 2/3 and 5, despite the large difference in the postmigratory ages of the two layers. By the end of the second postnatal week, the adult number of collaterals was achieved. Further elaboration of the local arbors occurred by repeated branching of already existing collaterals, rather than by addition of new collaterals to the main axon. These results demonstrate that the formation of local connections between cortical layers is highly specific, in contrast to the development of clustered horizontal connections by these same cells within layers 2/3 and 5, which involves extensive remodelling of local connections.     

Evidence for Excitatory Amino Acid Neurotransmitters in Forward and Feedback Corticocortical Pathways within Rat Visual Cortex

It is a commonly accepted notion that cells which make projections between the multiple cortical areas found in the mammalian visual system are excitatory, but there is little direct evidence that this is the case. Here we demonstrate using retrograde tracing with D-[³H]aspartate that connections in the rat which project from lower to higher visual areas (i.e. forward) and those which project from higher to lower areas (i.e. feedback) may use excitatory amino acid neurotransmitters. Following injection into the primary visual cortex, clusters of retrogradely labelled cells were found in several extrastriate areas within the cytoarchitectonic subdivisions 18a (‘areas’ LM, AL, PX, FLX, RL, AX) and 18b (‘area’ MX), and in the retrosplenial cortex. In all of these areas D-[³H]aspartate-labelled cells were surrounded by diffuse label which may represent anterograde labelling of axon terminals. This suggests that both legs of reciprocal intracortical circuits have similar chemospecificity. To directly demonstrate excitatory amino acid localization in forward projections, D-[³H]aspartate was injected into extrastriate area LM. As expected, the results revealed retrogradely labelled neurons within area 17. Outside area 17, LM injections labelled neurons in AL, PX, FLX, RL, AX and MX. Taken in the context of the hierarchy of areas in rat cerebral cortex (Coogan and Burkhalter, J. Neurosci., 13, 3749–3772, 1993), these results show that D-[³H]aspartate labels: (1) forward connections from area 17 to LM, AL, PX, RL, AX and MX, (2) feedback connections from LM, AL, FLX, PX, RL, AX and MX to area 17, (3) feedback connections from AL, PX, RL, AX and MX to LM, and (4) lateral connections between FLX and LM. These findings strongly indicate that both forward and feedback connections as well as lateral connections at several different levels of the cortical hierarchy use excitatory amino acid neurotransmitters.     

Relationship Between Lateral Inhibitory Connections and the Topography of the Orientation Map in Cat Visual Cortex

The functional and structural topography of lateral inhibitory connections was investigated in visual cortical area 18 using a combination of optical imaging and anatomical tracing techniques in the same tissue. Orientation maps were obtained by recording intrinsic signals in regions of 8.4–19 mm². To reveal the inhibitory connections provided by large basket cells, biocytin was iontophoretically injected at identified orientation sites guided by the pattern of surface blood vessels. The axonal and dendritic fields of two retrogradely labelled large basket cells were reconstructed in layer III. Their axonal fields extended up to 1360 μm from the parent somata. In addition to single basket cells, the population of labelled basket cell axons was also studied. For this analysis anterogradely labelled basket axons running horizontally over 460–1280 μm from the core of an injection site in layer III were taken into account. The distribution of large basket cell terminals according to orientation preferences of their target regions was quantitatively assessed. Using the same spatial resolution as the orientation map, a frequency distribution of basket cell terminals dependent on orientation specificity could be derived. For individual basket cells, the results showed that, on average, 43% of the terminals provided input to sites showing similar orientation preferences (±30°) to those of the parent somata. About 35% of the terminals were directed to sites representing oblique-orientation [±(30–60)°], and 22% of them terminated at cross-orientation sites [±(60–90)°]. Furthermore, the possible impact of large basket cells on target cells at different distances and orientation preferences was estimated by comparing the occurrence of orientation preferences with the occurrence of basket terminals on the distance scale. It was found that a basket cell could elicit iso-orientation inhibition with a high impact between 100–400 and 800–1200 μm strong cross-orientation inhibition at ～400–800 μm, and oblique-orientation inhibition between 300–500 and 700–900 μm from the parent soma. The non-isotropic topography of large basket axons suggests a complex function for this cell class, possibly including inhibition related to orientation and direction selectivity depending on the location of the target cells and possible target selectivity.     

Influences of Horizontal Connections on Visual Responses in Rabbit Striate Cortex

The goal of this study was to examine the role of horizontal connections in rabbit striate neurons. Anaesthetized rabbits were prepared in the usual fashion for single-cell recordings in area 17 of the visual cortex. We compared responses evoked by moving and stationary stimuli prior to, during and after recovery from lateral microinjection of either lidocaine ( n = 61), γ-aminobutyric acid (GABA, n = 18) or bicuculline ( n = 8) 2 mm from the recording site. This procedure allows evaluation of the contribution of neighbouring neurons in visual responses. Results showed that striate neurons are dependent on the adjacent cells¹ excitability. Modification of responses to stationary targets suggests that lateral interactions play a role in the generation of discharges to fixed stimuli. Lateral inactivation preferentially influenced non-directional over direction-selective units. This influence usually resulted in the non-directional neuron becoming directional by attenuation of the visually driven response in one direction. Simple and complex cells tended to be influenced differently by lateral inactivation. Simple cells became less responsive, whereas complex cells became more responsive. This dichotomy among cellular types suggests that simple cells receive mainly excitatory horizontal influences, while complex cells are contacted mostly by lateral inhibitory inputs.     

Projections from Areas 18 and 19 to Cat Striate Cortex: Divergence and Laminar Specificity

The results of electrical stimulation experiments [Bullier et al., (1988) Exp. Brain Res., 70, 90 - 98] demonstrated that afferents from areas 18 and 19 contact different functional types of neurons in area 17. We were therefore interested in examining whether these results could be explained by differences in the morphology of the terminals of these two groups of afferent connections to area 17. We also wanted to confirm, by a direct method, our earlier results [Salin et al. (1989) J. Comp. Neurol., 283, 486 - 512] that cortical afferents to area 17 in the cat present extensive divergences. We therefore placed small injections of anterograde tracers in areas 18 and 19 and examined the laminar distributions of terminals thus revealed and the extent of the surface of area 17 contacted by these terminals. Three tracers were used: wheat germ agglutinin - horseradish peroxidase (WGA - HRP), Phaseolus vulgaris leucoagglutinin (Pha-L) and biocytin. The results show that the divergence of these afferent connections are very extensive: 7 - 8 mm in the rotrocaudal direction and 3.5 - 6 mm in the mediolateral direction. In other words, neurons located in a region a few hundreds micron wide in areas 18 or 19 contact a region of area 17 covering several millimeters. Corticocortical connections are therefore not organized in a point-to-point fashion but are strongly divergent. The laminar distributions of terminals from areas 18 and 19 displayed a specific pattern. Area 19 projects most heavily to layers 5 and 6, also terminates in layers 1 - 3 and very little is present in layer 4. In contrast, the afferent terminals from area 18 are heaviest in layers 1, 2, 3, 4A and 5 and are rare in layer 6. Injections placed at different depths in area 18 revealed that upper layer neurons in that area mostly project to layers 1, 2, 3 and 5 in area 17, whereas lower layer neurons send their heaviest projections to layers 4A, 5 and 6 and hardly project to layers 1, 2 and 3.     

MAP2 Isoforms in Developing Cat Cerebral Cortex and Corpus Callosum

The microtubule-associated protein MAP2 was studied in the developing cat visual cortex and corpus callosum. Biochemically, no MAP2a was detectable in either structure during the first postnatal month; adult cortex revealed small amounts of MAP2a. MAP2b was abundant in cortical tissue during the first postnatal month and decreased in concentration towards adulthood; it was barely detectable in corpus callosum at all ages. MAP2c was present in cortex and corpus callosum at birth; in cortex it consisted of three proteins of similar molecular weights between 65 and 70 kD. The two larger, phosphorylated forms disappeared after postnatal day 28, the smaller form after day 39. In corpus callosum, MAP2c changed from a phosphorylated to an unphosphorylated variant during the first postnatal month and then disappeared. Immunocytochemical experiments revealed MAP2 in cell bodies and dendrites of neurons in all cortical layers, from birth onwards. In corpus callosum, in the first month after birth, a little MAP2, possibly MAP2c, was detectable in axons. The present data indicate that MAP2 isoforms differ in their cellular distribution, temporal appearance and structural association, and that their composition undergoes profound changes during the period of axonal stabilization and dendritic maturation.     

Functional and Structural Topography of Horizontal Inhibitory Connections in Cat Visual Cortex

The functional organization of long-horizontal inhibitory connections was studied in cat visual cortical area 17, using a combination of electrophysiological recording and anatomical tracing in the same tissue. Orientation maps were obtained by recording multiunit activity from layer III at regular intervals (100–300μm) in a region of -1.3 mm² of cortex at a depth corresponding to the location of the basket cell axons reconstructed later. Before the physiological mapping, the neuronal tracer biocytin had been iontophoretically injected at one functionally characterized site. On the basis of light microscopic features a total of five biocytin-labelled large basket axons, BC1 - BC5, were reconstructed from series of horizontal sections of two cats. The parent somata and dendritic fields of three axons (BC1, BC4 and BC5) could also be reconstructed. The axonal field of basket cell BC1 had an overall lateral spread of 1.8 mm. The axons of basket cells BC4 and BC5 spanned a distance of 3.05 and 2.85 mm, respectively. The distribution pattern of histologically reconstructed recording sites and of five labelled basket cell axons were directly compared in the same sections. The results show that a single large basket cell provides input to regions representing the whole range of orientations, i.e. iso-orientation (±30^°), oblique orientation (±[30–60]^°) and cross-orientation (±[60–90]^°) to that at the basket cell's soma. Furthermore, the differential effect mediated by the same large basket cell at sites of different orientation preference was numerically estimated for two basket cells (BC4 and BC5) whose preferred orientations could be determined on the basis of recording sites adjacent to their parent somata. We counted the number of axonal terminals of these basket cells at iso-, oblique- and cross-orientation sites and found no significant difference in the average density of terminals at sites of either orientation preference. The functional topography of large basket cell axons indicates that the same basket cell can mediate iso-, oblique- and cross-orientation inhibition at different sites. Hence, we assume that large basket cells serve a complex physiological role depending on the location of target cells in the orientation map.     

Organization of association projections from area 17 to areas 18 and 19 and to suprasylvian areas in the cat's visual cortex.

Cells in area 17 that are labelled by single, discrete injections of retrogradely transported tracers into extrastriate visual areas are discontinuously distributed in dense patches. In this study we made multiple, closely spaced injections of fluorescent dyes into extrastriate areas, to generate large deposits that would reveal whether the distributions of corticocortical cell bodies in area 17 are truly patchy or appear clustered only after small injections. By injecting a different tracer into each extrastriate area, or group of areas, we examined the spatial relationships between the populations of association cells. All deposits of tracers in areas 18, 19, or suprasylvian cortex, irrespective of size, label cells in a series of clusters in topographically related parts of area 17. We conclude that the complete populations of cells in area 17 that project to areas 18, 19, and the lateral suprasylvian cortex are all genuinely distributed in a patchy fashion. There appears to be a complex relationship between the sets of association cells projecting to different extrastriate regions: they do not completely overlap, only partially, and share some cortical zones but not others. In these experiments, only tiny percentages (2-5%) of labelled cells in the overlapping regions were filled with both tracers, suggesting that very few association cells in area 17 project to more than one of the extrastriate areas we studied. By comparing the dimensions of each injection site and of the labelled region in area 17, we estimated the extent of the convergence from area 17 to areas 18, 19, and posteromedial suprasylvian areas in retinotopic terms. The functional convergence was very similar in these pathways.     

Transient cortical pathways in the pyramidal tract of the neonatal ferret

Anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to study transient axons from the visual cortex in the pyramidal tract. Injections at birth restricted to the visual cortex labeled axons in the vicinity of the pontine nuclei. Two to eight days after birth, axons from the occipital cortex were found posterior to the pontine nucleus, their caudalmost stable target. Transient corticospinal axons from the presumptive primary visual cortex did not grow caudal to the pyramidal decussation. Innervation of more distal targets preceded innervation of proximal targets. Innervation of the pontine nucleus is initiated around 68 hours after birth, when the transient extension in the medullary pyramidal tract has attained its maximum caudal extent. Innervation of the superior colliculus begins 9 days after birth. Retrograde tracers were used to follow the developmental changes in the cortical distribution of the parent neurons giving rise to axons in the pyramidal tract. In the adult, labeled neurons following injection of retrograde tracer in the pyramidal tract occupied less than a third of the neocortex and were centred on the anterior part of the coronal and spleniocruciate gyri. In the immature brain, labeled neurons covered more than two-thirds of the neocortex. Areal density measurements in the neonate showed that peak labeling was centred in the anterior coronal and spleniocruciate gyri, where corticospinal cells in the adult are located. There was a marked rostral-caudal gradient so that labeled neurons were very scarce towards the occipital pole. These results, showing transient neocortical axons in the pyramidal tract in a carnivore, suggest that this may be a common feature of mammalian development. The finding that the adult pattern of corticospinal projections does not emerge from a uniform distribution is discussed with respect to the areal specification of cortical connectivity. © 1993 Wiley-Liss, Inc.     

Cytochemical Redistribution of 5'-Nucleotidase in the Developing Cat Visual Cortex

The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol. , 296 , 379 – 392, 1990). Using an enzyme-cytochemical technique, we now investigate the developmental redistribution of 5'-nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5'-nucleotidase at synapses parallels the time-course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse-bound 5'-nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme.     

Differential Distribution of Tau Proteins in Developing Cat Cerebral Cortex and Corpus Callosum

During the postnatal development of cat visual cortex and corpus callosum the molecular composition of tau proteins varied with age. In both structures, they changed between postnatal days 19 and 39 from a set of two juvenile forms to a set of at least two adult variants with higher molecular weights. During the first postnatal week, tau proteins were detectable with TAU-1 antibody in axons of corpus callosum and visual cortex, and in some perikarya and dendrites in the visual cortex. At later ages, tau proteins were located exclusively within axons in all cortical layers and in the corpus callosum. Dephosphorylation of postnatal day 11 cortical tissue by alkaline phosphatase strongly increased tau protein immunoreactivity on Western blots and in numerous perikarya and dendrites in all cortical layers, in sections, suggesting that some tau forms had been unmasked. During postnatal development the intensity of this phosphate-dependent somatodendritic staining decreased, but remained in a few neurons in cortical layers II and III. On blots, the immunoreactivity of adult tau to TAU-1 was only marginally increased by dephosphorylation. Other tau antibodies (TAU-2, B19 and BR133) recognized two juvenile and two adult cat tau proteins on blots, and localized tau in axons or perikarya and dendrites in tissue untreated with alkaline phosphatase. Tau proteins in mature tissue were soluble and not associated with detergent-resistant structures. Furthermore, dephosphorylation by alkaline phosphatase resulted in the appearance of more tau proteins in soluble fractions. Therefore tau proteins seem to alter their degree of phosphorylation during development. This could affect microtubule stability as well as influence axonal and dendritic differentiation.     

The Perceptual Grouping Criterion of Colinearity is Reflected by Anisotropies of Connections in the Primary Visual Cortex

An important step in the processing of visual patterns is the segmentation of the retinal image. Neuronal responses evoked by the contours of individual objects need to be identified and associated for further joint processing. These grouping operations are based on a number of Gestalt criteria. Here we report that connections in the visual cortex of the cat exhibit a highly significant anisotropy, preferentially linking neurons activated by contours that have similar orientation and are aligned colinearly. These anatomical data suggest a close relation between the perceptual grouping criterion of colinearity and the topology of tangential intracortical connections. We propose that tangential intracortical connections support perceptual grouping by modulating the saliency of distributed cortical responses in a context-dependent way. The present data are compatible with the hypothesis that the criteria for this grouping operation are determined by the architecture of the tangential connections.     

Transient Association of the HNK-1 Epitope with 5'-Nucleotidase during Development of the Cat Visual Cortex

During early postnatal development of the kitten visual cortex the ectoenzyme 5'-nucleotidase undergoes a characteristic redistribution. Until about postnatal week 6 it is essentially confined to synaptic contacts in input layer IV and its expression is related to the use-dependent segregation of thalamic afferents into ocular dominance columns. Subsequently, 5'-nucleotidase becomes distributed uniformly throughout all layers and is then associated selectively with glial cells. Here we describe an age-dependent alteration in the expression of a carbohydrate epitope of 5'-nucleotidase which correlates with the developmental change of the enzyme's localization. We have isolated 5'-nucleotidase from the occipital cortex of kittens of varying age and from adult cats and investigated by immunoblotting the association of the HNK-1 carbohydrate epitope with the protein. 5'-Nucleotidase carries the HNK-1 epitope in kittens of 3–9 weeks but the epitope is absent from 12-week-old kittens or adult cats. Thus, the appearance of the HNK-1 epitope correlates with the transient localization of the enzyme at synapses. The HNK-1 carrying 5'-nucleotidase may be involved in synaptogenesis and use-dependent modifications of synaptic connections.     

The organization of immature callosal connections

In newborn kittens, the anterograde transport of horseradish peroxidase, alone or bound to wheat-germ agglutinin, indicates that callosal axons have entered selectively the restricted portions of the neocortical gray matter (e.g., the area 17/18 border) which receive callosal afferents in adults. The callosal axons do also reach regions where they lack in the adult, but there they seem not to penetrate far into the gray matter. Neonatal injections of retrograde fluorescent tracers restricted to the gray matter in areas 17, 18, and posteromedial lateral suprasylvian area (PMLS) label neurons in the contralateral hemisphere only when the tracers were directed into regions known to receive callosal axons. In particular, injections near the 17/18 border label neurons in the contralateral hemisphere at the homologous site and at restricted, retinotopically corresponding locations in other visual areas: a pattern similar to the adult one. In contrast, an injection reaching the white matter of areas 17 or 18 labels a wider, continuous territory extending mediolaterally over most visual areas from 17 to posterolateral lateral suprasylvian area (PLLS) and including regions which later become acallosal; in addition, labeled neurons are found in the limbic cortex medial to area 17 and in the auditory cortex lateral to PLLS, none of which is known to project to either 17 or 18 in the adult. In flattened reconstructions of the cortex, the shape of the territory labeled by each of these injections is characteristically, although somewhat irregularly, crescent shaped; its rostrocaudal position varies with that of the injection. An injection extending into the white matter of more lateral visual areas (19, 21a, PMLS) labels callosal neurons over a similar territory, which extensively overlaps that labeled by the 17/18 border injections and likewise includes regions which are acallosal in the adult. In spite of the overlapping distribution of labeling obtained from separate injection sites, as in adults, each cytoarchitectonically (or retinotopically) defined area seems to receive from a different set of neurons, although a few neurons send bifurcating axons to more than one area. In conclusion, injections restricted to the cortical gray matter reveal a topographic organization of juvenile callosal connections similar to that of the adult. In contrast, injections extending into the white matter and adequate to reach the transitory callosal axons which appear to be confined there reveal what appears to be an earlier organization. These two organizations probably reflect different morphogenetic factors.     

Effects of Visual Cortex Lesions on Orientation Discrimination of Illusory Contours in the Cat

We have trained five cats in orientation discrimination using different contours, and compared the deficits caused by lesions of cortical areas 17 and 18 (tier I) to the deficits induced by removal of those areas receiving afferents originating in areas 17 and 18 (tier II). As contour stimuli we used two types of illusory contours and a luminance bar. The two illusory contours were defined by opposed line-ends. One of them coincided with a luminance gradient whereas the other did not. Tier I lesions destroyed the capacity to discriminate the orientation of both illusory contours, and also caused an important, though less severe, deficit in bar orientation discrimination. The deficits induced by tier I lesions were permanent. Tier II lesions also caused significant deficits in orientation discrimination of illusory contours, but only a negligible deficit in bar orientation discrimination, and this result was not a mere consequence of a difference in difficulty between the tasks involving bars and illusory contours. In addition, tier II lesions differentiated between illusory contour types, the deficit being more pronounced for the illusory contour without luminance gradient than for the one with luminance gradient. In contrast to tier I lesions, tier II lesions allowed significant recovery, leading to small final deficits for all contour types tested.