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Neurons with callosal projections in visual areas of newborn kittens: an analysis of their dendritic phenotype with respect to the fate of the callosal axon and of its target.

Combined retrograde transport of Rhodamine-labeled latex beads and intracellular injection of Lucifer Yellow in aldehyde-fixed slices of areas 17 and 18 in kittens indicate that neurons with similar dendritic morphology send axons into the corpus callosum from the 17/18 border and from parts of area 17 destined to become acallosal. At both sites callosally projecting neurons (callosal neurons) include pyramids, spiny stellate cells and star-pyramids; two types of pyramidal neurons can be distinguished on the basis of the complexity of their apical dendrites. At both sites, the dendritic morphology of callosal neurons appears basically unaffected by the ablation at the beginning of the second postnatal week of the contralateral areas 17 and 18 to which they have sent their axon. Thus the dendritic morphology of this type of cortical neuron seems independent of retrograde signals coming from their contralateral target and may instead depend on "programs" intrinsic to the neurons and/or conditions acting locally on their cell bodies, dendrites or initial axon collaterals.

Animals

The callosal system of the superior parietal lobule in the monkey.

The callosal connections of the superior parietal lobule, area 5 of Brodmann, were studied in macaque monkeys (M. nemestrina and M. fascicularis) using anatomical techniques based on both anterograde and retrograde axoplasmic transport of wheat-germ-agglutinin-conjugated horseradish peroxidase. From sagittal sections, two-dimensional flattened computer reconstructions of the volumes of cortical tissue containing callosal-projecting neurons (callosal efferent zone) and/or callosal terminal axons (callosal terminal territory) were obtained. Callosal zones were found in area 5, including the supplementary sensory area, in a limited part of area 6, i.e., in the supplementary motor area, in area 7b, in the cortex of the dorsal bank of the sylvian fissure, and in a limited part of area 7a, in the cortex of the upper third of the rostral bank of the superior temporal sulcus. Callosal neurons in all cortical areas studied, though with regional variations, predominated in layer IIIb, but were also very numerous in layers VI and V. They were rare in other cortical laminae. In the cortical regions projecting heterotopically to area 5, the tangential distribution of callosal neurons was discontinuous because of the presence of large acallosal regions. These were not observed in area 5, although here the distribution of callosal neurons waxed and waned in the tangential cortical plane. Callosal axons to and/or from area 5 crossed the midline in the posterior, presplenial part of the corpus callosum. In the superior parietal lobule they terminated in radial patches or columns, spanning layers I-IV. These columns of various width (200-2,000 micron) were separated by gaps of similar size, free of such terminals. Callosal neurons were present not only within, but also between, the callosal terminal columns. Callosal neurons located within the callosal terminal columns were, in a statistically significant way, more numerous than those located between them. The callosal efferent zone occupied 71% of the tangential domain of area 5, whereas the callosal terminal territory occupied only 49% of it. This difference is statistically significant. The discontinuous columnar arrangement of callosal terminals and the periodic distribution of callosal neurons in the lateral part of area 5 defined three main bands of callosal connections of irregular shape which were oriented mediolaterally and ran parallel to the main architectonic borders, the border between areas 2 and 5 and that between 5 and 7.

Animals

Development of visual callosal connections in neonatally enucleated rats.

The present report extends previous descriptions of the mature distributions of callosal cells and axonal terminations in rats monocularly or binocularly enucleated at birth. It also describes the time course of callosal development in these animals, and establishes the age at which eye removal ceases to alter the normal course of callosal development. Although our results indicate that the callosal pattern is anomalous in adult, neonatally enucleated rats, the major features of the normal callosal pattern are nonetheless clearly recognizable in both monocularly and binocularly enucleated rats. Thus, as in normally reared rats, there are dense accumulations of callosal cells and terminations at the 17/18a border region, at the lateral border of area 18a, and within area 18b in enucleated rats. In addition, several narrow bands of callosal connections bridge the width of area 18a at several rostrocaudal levels, and a ring-like callosal configuration is located anterolateral to area 17. In monocularly enucleated rats, the most prominent anomaly develops in the hemisphere ipsilateral to the remaining eye, where a dense band of callosal connections runs rostrocaudally through the center of area 17. Periodic fluctuations in the density of labeling along the length of this extra band give it a beaded appearance. The callosal pattern in the hemisphere contralateral to the remaining eye in these rats appears normal. Binocular enucleation causes the appearance of discrete regions of reduced labeling within the 17/18a callosal band and several densely labeled tongue-like regions that extend medially from this band well into area 17. The laminar distribution of callosal cells and terminations is not significantly altered by loss of one or both eyes at birth. Our data indicate that enucleation does not affect the time course of callosal development. Thus, in enucleated pups, all features of the mature callosal pattern can be recognized by 6-7 days of age, and by 12 days of age the patterns appear virtually mature. Finally, our data reveal that monocular or binocular enucleations performed at 6 days of age or later allow the callosal pattern to develop normally, whereas enucleations performed between birth and 5 days of age produce anomalies similar to those observed in rats enucleated at birth. Thus, at about 6 days of age--just as the earliest features of the mature callosal pattern become discernible, and long before rats first open their eyes--the developing callosal pathway is no longer susceptible to disruptions of visual input.

Age Factors

Development of callosal connections in the sensorimotor cortex of the hamster.

To investigate the development of corpus callosal connectivity in the hamster sensorimotor cortex, we have used the sensitive axonal tracer 1,1 dioctadecyl-3,3,3',3', tetramethylindocarbocyanine perchlorate (DiI), which was injected either in vivo or in fixed brains of animals 3-6 days postnatal. First, to study changes in the overall distribution of developing callosal afferents we made large injections of DiI into the corpus callosal tract. We found that the anterogradely labeled callosal axons formed a patchy distribution in the contralateral sensorimotor cortex, which was similar to the pattern of adult connectivity described in earlier studies of the rodent corpus callosum. This result stands in contrast to previous retrograde studies of developing callosal connectivity which showed that the distribution of callosal neurons early in development is homogeneous and that the mature, patchy distribution arises later, primarily as a result of the retraction of exuberant axons. The initial patchy distribution of callosal axon growth into the sensorimotor cortex described in the present study suggests that exuberant axons destined to be eliminated do not enter the cortex. In addition, small injections of DiI into developing cortex resulted in homotopic patterns of callosal topography in which reciprocal regions of sensorimotor cortex are connected, as has been shown in the adult. Second, to study the radial growth of callosal afferents we followed the extension of individual callosal axons into the developing cortex. We found that callosal axons began to invade the contralateral cortex on about postnatal day 3, with little or no waiting period in the callosal tract. Callosal afferents then advanced steadily through the cortex, never actually invading the cortical plate but extending into layers on the first day that they could be distinguished from the cortical plate. The majority of callosal axons grew radially through the cortex and did not exhibit substantial branching until postnatal day 8, the age when the cortical plate disappears and callosal afferents reach the outer layer of cortex. This mode of radial growth through cortex prior to axon branching could serve to align callosal afferents with their radial or columnar targets before arborizing laterally.

Anesthesia

Organization and postnatal development of callosal connections in the visual cortex of the rat.

The distribution of callosal cells and terminals was studied in the posterior neocortex of pups whose ages ranged from 3 to 16 days and in adult rats 2 months of age or older. Callosal cells and terminations were revealed using retrograde (horseradish peroxidase) and anterograde (horseradish peroxidase; tritiated proline) tracing techniques, respectively, and the distribution of callosal connections was analyzed in tangential or coronal histological sections. In agreement with previous studies, we observed that the pattern of callosal connections in areas 17 and 18 of adult rats contains the following features: (1) a dense band of callosal cells and terminations separating the interiors of areas 17 and 18a, (2) a ringlike configuration anterolateral to area 17, (3) a region of dense labeling lateral to area 18a, (4) several narrow bands of labeling that bridge area 18a at different anteroposterior levels, and (5) one or more labeled regions in area 18b. In all these callosal regions, labeled cells and terminations are densely aggregated in layers II-III, Va, and Vc-VIa, and less densely in layer IV and the remaining portions of layers V and VI. High densities of isotope-labeled fibers are also observed in the lower half of layer I. Throughout the interiors of areas 17 and 18a, a significant number of labeled cells are observed in layers Vc-VIa. In contrast to adult rats, in neonates no distinct tangential pattern of callosal connections is apparent. Instead, labeled cells are densely aggregated in two continuous horizontal bands located in cortical layers Va and Vc-VIa, and callosal axons are largely restricted to white matter. During the first 2 postnatal weeks there is a progressive loss of callosal cells in regions that normally have few callosal cells in the adult (e.g., interiors of areas 17 and 18a) and an increase in the number of cells in layers II-IV in regions that are densely callosal in the adult (e.g., callosal regions at the 17/18a border, lateral border of area 18a, and in area 18b). The decrease in the number of callosal cells in the interiors of areas 17 and 18a is more severe in the upper than in the lower band of the immature labeling pattern, and our data from tangential sections indicate that this loss of callosal neurons occurs synchronously across the interiors of these areas. During this period there is also a localized invasion of labeled callosal axons into those regions of gray matter where they will be found in adult life.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Synaptic connections of callosal projection neurons in the vibrissal region of mouse primary motor cortex: an electron microscopic/horseradish peroxidase study.

Reciprocal axonal projections between homotypic areas of the vibrissal region of mouse primary motor cortex (MsI) (Porter and White: Neurosci. Lett. 47:37-40, '84) suggested the existence of reciprocal synaptic connections between callosal projection neurons and callosal afferents. In the present study, the retrograde transport of horseradish peroxidase (HRP) was combined with lesion-induced degeneration to identify synapses between callosal afferents and callosal neurons in the corresponding region of the contralateral cortex. The procedure was as follows: MsI was injected with HRP and aspirated on the following day. After 4 days, the animals were perfused and motor cortex was processed for HRP according to a variation of the Adams (Brain Res. 176:33-47,'77) technique, and postfixed in OsO4. The methods used consistently filled fine dendritic branches and spines with dense reaction product, thus allowing examination of synaptic contacts with these processes. All callosal projection neurons were identified as pyramidal neurons, having somata in cortical layers II/III and V. Labeled cells from each of the two levels were prepared for electron microscopy, and that part of each cell's apical dendrite that traversed the superficial cortical layers, where most callosal axons terminate, was cut in an unbroken series of thin sections. Micrographs were taken of all labeled profiles in each thin section, and tracings of the profiles were assembled to reconstruct the apical dendrites. Data on the distribution, type, and amount of callosal and other synapses with the shaft and spines of the apical dendrites were obtained by examining the reconstructions. In addition, profiles of basal dendrites of layer II/III cells were examined in thin sections to ascertain the numbers of callosal and other synapses formed with their shafts and spines. The proportion of synapses that each dendrite formed with callosal axon terminals was compared to the concentration of callosal afferents in the neuropil. Dendrites of both layer II/III and layer V pyramidal cells synapsed with callosal axon terminals. The apical and basal dendrites of layer II/III neurons formed a similar proportion of their synapses with callosal afferents, and this was similar to the concentration of callosal synapses in the surrounding neuropil. Segments of apical dendrites belonging to layer V and layer II/III neurons course through neuropil containing nearly the same concentration of degenerating callosal terminals, but the layer V cells form fewer callosal synapses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Topography of interhemispheric connections in neocortex of mice with congenital deficiencies of the callosal commissure.

Normally, axons within the corpus callosum are ordered according to the cortical regions from which they originate, and callosal cells and terminations form elaborate cortical patterns related to the underlying topographic representations of the sensory periphery. About 30% of mice of the BALB/c strain show congenital deficiencies of the callosal commissure which range from total absence of the corpus callosum to a moderate reduction in the size of this commissure. In the light of current theories about the origin of these callosal deficiencies, it seems likely that fibers crossing the midplane in mutant mice have to circumvent local disturbances along their migration path. Since these disturbances in fiber trajectory may, in turn, alter the overall pattern of callosal projections, we set out to investigate whether the distribution of callosal connections in mice with marked deficiencies of the corpus callosum is as ordered as in normal mice. In groups of normal and mutant mice, we used multiple injections of horseradish peroxidase to reveal the overall distribution of callosal connections and restricted injections of horseradish peroxidase conjugated with wheat germ agglutinin to reveal finer aspects of the organization of the callosal pathway in these animals. Our results show that the number of labeled cells is reduced in mice with a small corpus callosum and that no labeled cells are present in the neocortex of acallosal mice. Furthermore, the topographic distribution of fibers within the corpus callosum of mutant mice can be significantly less ordered than in normal mice. However, even in mice with extreme deficiencies of the corpus callosum, callosal fibers originate from and terminate in all major areas of the cortex, and, within these areas, callosal cells and terminations are distributed according to the normal plan. The laminar distribution of callosal cells also appears normal in these mice. These findings indicate that gross developmental anomalies of the corpus callosum do not prevent normal specification of the callosal pattern during development. Within the context of current theories about the origin of congenital callosal deficiencies, our findings suggest that callosal fibers are able to establish appropriate contralateral connections in spite of alterations of their migration route. They also suggest that fiber topography within the corpus callosum does not play an important role in guiding migrating axons to their correct contralateral targets. Finally, our failure to find labeled fibers within the anterior commissure indicates that this commissure does not serve as an alternative route for deviated callosal axons.

Agenesis of Corpus Callosum

Organization of callosal connections in the visual cortex of the rabbit following neonatal enucleation, dark rearing, and strobe rearing.

The organization of visual callosal projections was studied in (1) normal adult rabbits; (2) adult rabbits which had undergone monocular enucleation (ME) or binocular enucleation (BE) at birth; and (3) adult rabbits which had been deprived of normal visual experience during development by dark rearing (DR) or strobe rearing (SR). Previously published observations (Murphy and Grigonis, Behav Brain Res 30:151, 1988) on callosal organization in adult rabbits in which retinal ganglion cell activity was eliminated during development by intraocular tetrodotoxin (TTX) injections, are also summarized for comparison with these data. The tangential extent of the callosal cell zone was significantly larger than normal in DR, TTX, and ME rabbits, was unchanged in BE rabbits, and was significantly reduced in SR rabbits. An analysis of the laminar distribution of the callosal cells revealed a significant increase in the percentage of callosal cells in lamina IV in ME, DR, and TTX animals. Measurements of density of callosal cells showed a significant increase in the density of the callosal projection in ME and SR rabbits and a decrease in density in BE rabbits compared with normal. The data suggest that the mechanisms involved in the development of the tangential and laminar organization of the callosal cell zone are different. In addition, the data suggest that the mechanisms involved in the maintenance of callosal projections are different from the mechanisms involved in the elimination of callosal projections during development. The effects of these developmental manipulations on callosal organization in other mammals are reviewed and compared with the effects in rabbits. The data suggest that species differences in the degree of maturity of the visual system at birth and in the extent of callosal development at the time of eye opening, may underlie species differences in the effects of these manipulations on the organization of visual callosal projections during development.

Animals

The anatomical substrate of callosal messages from SI and SII in the cat.

Horseradish peroxidase (HRP) was injected into the first (SI) or second (SII) somatosensory areas of 21 adult cats. The radial and tangential (normal and parallel to the pial surface, respectively) distribution and morphology of the callosal neurons were studied. HRP injections were combined with single unit recording in the contralateral cortex in order to determine which part of the somatosensory periphery is represented within the regions containing callosal neurons, the callosal (efferent) zones, in SI and SII. The callosal zone of SI extends over the trunk and part of the forepaw representation. In the forepaw and hindlimb representations callosal neurons projecting only to the contralateral SII are found, while in the trunk representation callosal neurons projecting to contralateral SI or SII are found. The callosal zone in SII extends widely throughout the forepaw representation in this area and projects to the contralateral SII but not to SI. In both SI and SII the callosal neurons are mainly located in layer III. A few of them are also found in layer VI. They are very rare in other layers. Callosal neurons in layer III are mostly pyramidal but exceptionally stellate; in layer VI they are pyramidal, triangular, and occasionally stellate. These data indicate that transformations of the cortical somatosensory maps are achieved in the message sent through the corpus callosum. These transformations are i) determined by the extent and location of the callosal zones and perhaps by the distribution of callosal neurons within them, ii) different in different areas, iii) different in a same area, according to the cortical targets to which they are conveyed. The existence of callosal connections originated from areas of distal forepaw representation supplies a possible anatomical substrate for those types of intermanual transfer of tactile learning which depend upon the integrity of the corpus callosum.

Animals

Ontogenetic change in the distribution of callosal projection neurons in the postcentral gyrus of the fetal rhesus monkey.

In the postcentral gyrus of the mature rhesus monkey the distribution of callosal projection neurons is discontinuous. The density of callosal projection neurons, which are mainly located in the supragranular layers, varies both within and across cytoarchitectonic areas (Killackey et al., '83). In the present study, we investigated the ontogeny of corpus callosum projections of the postcentral gyrus in five fetal rhesus monkeys, ranging in age from embryonic day (E) 108 to E 133. Multiple large injections of horseradish peroxidase that involved the underlying white matter were made into the postcentral gyrus of one hemisphere and the distribution of labeled neurons in the ipsilateral thalamus and the other hemisphere was determined. The pattern of thalamic label indicated that the tracer was effectively transported from all portions of the postcentral gyrus. We found that the areal distribution pattern of labeled callosal projection neurons varied at the different fetal ages. At early fetal ages (E 108, E 111, and E 119) callosal projection neurons were continuously distributed throughout the postcentral gyrus. As in the adult animal, the vast majority of labeled callosal projection neurons were found in the supragranular layers, although a few labeled cells were located in the infragranular layers. From the earliest age, there was regional variation in the width of the band of labeled supragranular callosal projection neurons. The difference between the precentral and postcentral gyrus was most obvious, but there was also a difference between anterior and posterior portions of the postcentral gyrus. The first indication of some discontinuity in the distribution of callosal projection neurons was noted at E 126. By E 133, approximately 1 month before birth, the distribution of callosal projection neurons appeared remarkably mature. On E 119 aggregations of anterograde label could be detected in restricted portions of the posterior postcentral gyrus beneath the cortical layers. By E 133 anterograde label was found within the cortical layers (most densely in layer IV) in these regions of the postcentral gyrus. Thus, the emergence of the discrete pattern of callosal projection neurons appears to be temporally correlated with the ingrowth of callosal afferents. On the basis of these observations, as well as those of others (discussed in the text), we propose that the ontogenetic changes in the distribution of callosal projection neurons reflect the unique strategy employed by cortical projection neurons in establishing their patterns of connectivity. It is hypothesized that this strategy may involve multiple processes.

Animals

Sources and terminations of callosal axons related to binaural and frequency maps in primary auditory cortex of the cat.

The distributions of sources and terminals of callosal fibers in the high-frequency representation of AI were related to binaural and frequency maps in combined anatomical and electrophysiological experiments. Sources of callosal axons were retrogradely labeled with HRP. Distributions of axon terminals were determined by autoradiographic labeling with [3H]-proline and anterograde degeneration following callosal section. Regions in which cells exhibit summation or ipsilateral dominance and suppression contain higher concentrations of sources and terminals of callosal fibers than do regions in which cells exhibit monaural contralateral responses or contralateral dominance and suppression. Callosal axon terminals aggregate into columns. In sections cut parallel to the cortical surface callosal columns take on complex forms that exhibit certain consistent features. Two prominent elongated columns separated by a narrow zone of sparse callosal innervation run in a rostrodorsal to caudoventral direction through AI crossing several octaves of the frequency representation. Ventral to these columns, along the AI-AII border, less densely labeled callosal columns are in evidence. Low frequency representations of AI are interconnected but details of their innervation patterns were not worked out. Outside of AI there are regions that contain complex configurations of callosal columns. Several morphologically distinct types of neurons, located in laminae III through VI, were retrogradely labeled following injections of HRP into the opposite AI. About 94% of callosal neurons are pyramidal cells of layers III and IV.

Animals

Callosal projections from area SII to SI in monkeys: anatomical organization and comparison with association projections.

The present research was aimed at ascertaining in the macaque monkey the reciprocity of the heterotopical callosal connections between SI and SII, with particular regard to the connectivity of the hand representation, and at comparing the topographical and laminar pattern of these callosal connections with those of association connections entertained by these areas. Horseradish peroxidase (HRP) was unilaterally injected into area SI in five monkeys. The sites of HRP delivery included the trunk and the hand zones preliminarily identified by recording multi-unit responses to peripheral stimulation by means of microelectrodes. Anterograde and retrograde labelling was studied in SII of both sides. The results showed the complete reciprocity of the heterotopical callosal connections between SI and SII. In the latter area both callosal axon terminals and neurones were found, which were labelled from either the trunk or the hand zone of contralateral SI. Labelling of callosal axon terminals occurred mainly in layer IV and in the lowermost part of layer III. Labelled callosal neurones were mainly in the lower half of layer III, whereas few occurred in infragranular layers. Topographically, the distribution of callosal terminals and cell bodies duplicated the distribution of association terminals and cell bodies labelled in SII on the side ipsilateral to HRP injection. The laminar pattern of termination of association fibres from SI was similar to that of callosal fibres. However, the distribution of association-projecting neurones in SII showed a striking difference from that of callosal-projecting neurones. Unlike the latter neurones, which were mainly located in supragranular layers, association cell bodies overwhelmingly dwelt in layers V and VI and were less numerous in layers II and III. This laminar pattern of association SII-SI cells corresponds to the "feed-backward" model and fits the laminar pattern of their axon terminations (Friedman: Brain Res. 273: 147-151, '83). The association and callosal inputs and outputs of area SII are discussed in relation to the function of the forward and backward type of reciprocal connections entertained with SI in the ipsilateral hemisphere and to the function of SII in the interhemispheric exchange of somatosensory information.

Animals

Callosal connections of the somatic sensory areas II and IV in the cat.

The homotopic and heterotopic callosal connections in the forelimb representations of the second (SII) and fourth (SIV) somatic sensory areas of cats were investigated by means of the axonal transport of horseradish peroxidase (HRP) in conjunction with microelectrode recording. The tracer was injected in the electrophysiologically identified hand and/or digit zone of SII (six cats) or SIV (four cats). The homotopic area in the contralateral hemisphere was explored with microelectrodes in five animals (three injected in SII and two in SIV) to map neuronal receptive fields. The aim was to correlate in the same experimental case the topography of labelled callosal neurons with the physiological map of the forelimb. Labelled cells and recording sites were plotted on planar maps reconstructed with the aid of a computer from serial coronal sections from the anterior ectosylvian gyrus. After SII injections, labelled callosal neurons were observed throughout the forelimb representation in the contralateral area, but in the tangential plane their distribution was uneven. Each somatotopic zone composing the forelimb map, that is, the arm, hand, and digit zones, contained several subzones in which callosal neurons were either dense or rare. Microelectrode explorations showed that receptive fields mapped from callosal and relatively acallosal subzones representing the same body part were similar in extent and location. After SIV injections, labelled callosal neurons were observed throughout the forelimb and proximal body representation of the contralateral area. Although slight regional variations in the density of labelled cells were apparent, no subzones bare of callosal labelling were observed in SIV. In both SII and SIV, callosal neurons were concentrated mainly in layer III, but a significant number was also evident in the infragranular layers. After HRP injections in the digit zone of SII or SIV, labelled cell bodies were also observed in heterotopic areas of the contralateral hemisphere. Most of these neurons were clustered in the medial bank of the coronal sulcus and in two other heterotopic cortical regions lying, respectively, in the anterior suprasylvian sulcus and in the lateral branch of the ansate sulcus. Some callosal cells interconnecting SII and SIV were also labelled. The results show that the distal forelimb zones in SII and SIV are callosally connected with the respective homotopic zones and with several somatosensory fields located heterotopically in the contralateral hemisphere.

Afferent Pathways

Maturation of the corpus callosum of the rat: I. Influence of thyroid hormones on the topography of callosal projections.

The normal adult rat corpus callosum contains numerous axonal profiles that are immunoreactive for the high molecular weight subunit of the neurofilament triplet (NF-H). NF-H immunoreactivity develops gradually during the first 2 postnatal weeks. The expression of NF-H immunoreactivity is almost completely suppressed in rats rendered hypothyroid by neonatal treatment with propylthiouracil. To ensure that the cytoskeletal deficit was due to a shortage of thyroid hormones rather than to unspecific, toxic effects of propylthiouracil, hypothyroid animals kept on the propylthiouracil diet were given restorative thyroxine injections daily. Such animals express NF-H at normal levels. This suggests that the callosal axons may be arrested at an immature stage of development. The immaturity of the hypothyroid corpus callosum can also be revealed by a comparison of the myelin content in the corpus callosum between normal rats, hypothyroid rats, and hypothyroid rats under thyroxine therapy. Hypothyroid rats are severely deficient in myelin, and again this deficit can be corrected by postnatal thyroxine treatment. During normal callosal development, there is a progressive spatial restriction of the transcallosal projection that creates in the adult patches of callosally projecting cortex interposed by acallosal regions. Given the structural immaturity of the hypothyroid callosal axons, it was interesting to investigate the state of development of their topography. For this purpose, multiple injections of wheat germ agglutinin-horseradish peroxidase were made into the occipital and parietal cortices of adult hypothyroid animals. In normal rats, the majority of visual callosally projecting cells are located in three groups--in area 18b, at the boundary of area 17 and 18a, and in the lateral portion of area 18a. Within these areas projecting cells are concentrated in layers II-III, Va, and Vc-VIa. The callosal axon terminals are concentrated in these same regions, with a laminar distribution as far as the somata plus layer I. In the midportion of areas 17 and 18a, fewer callosal cells are found, and they occupy mainly layers Vc-VIa, as in the case for terminals in these same areas. In the parietal cortex, callosal cells and terminals are disposed in vertical arrays alternating with almost empty zones. Most are concentrated in layers III and V. The topography of the callosal axon terminal fields is unaffected by hypothyroidism. However, there is a dramatic redistribution of the callosally projecting cell somata.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Topographic organization, number, and laminar distribution of callosal cells connecting visual cortical areas 17 and 18 of normally pigmented and Siamese cats.

The callosal connections between visual cortical areas 17 and 18 in adult normally pigmented and "Boston" Siamese cats were studied using degeneration methods, and by transport of WGA-HRP combined with electrophysiological mapping. In normal cats, over 90% of callosal neurons were located in the supragranular layers. The supragranular callosal cell zone spanned the area 17/18 border and extended, on average, some 2-3 mm into both areas to occupy a territory which was roughly co-extensive with the distribution of callosal terminations in these areas. The region of the visual field adjoining the vertical meridian that was represented by neurons in the supragranular callosal cell zone was shown to increase systematically with decreasing visual elevation. Thus, close to the area centralis, receptive-field centers recorded from within this zone extended only up to 5 deg into the contralateral hemifield but at elevations of -10 deg and -40 deg they extended as far as 8 deg and 14 deg, respectively, into this hemifield. This suggests an element of visual non-correspondence in the callosal pathway between these cortical areas, which may be an essential substrate for "coarse" stereopsis at the visual midline. In the Siamese cats, the callosal cell and termination zones in areas 17 and 18 were expanded in width compared to the normal animals, but the major components were less robust. The area 17/18 border was often devoid of callosal axons and, in particular, the number of supragranular layer neurons participating in the pathway were drastically reduced, to only about 25% of those found in the normally pigmented adults. The callosal zones contained representations of the contralateral and ipsilateral hemifields that were roughly mirror-symmetric about the vertical meridian, and both hemifield representations increased with decreasing visual elevation. The extent and severity of the anomalies observed were similar across individual cats, regardless of whether a strabismus was also present. The callosal pathway between these visual cortical areas in the Siamese cat has been considered "silent," since nearly all neurons within its territory are activated only by the contralateral eye. The paucity of supragranular pyramidal neurons involved in the pathway may explain this silence.

Albinism

Segregation and overlap of callosal and association neurons in frontal and parietal cortices of primates: a spectral and coherency analysis.

The spatial relations between selected classes of association and callosal neurons were studied in the frontal and parietal lobes of the macaque monkey using retrogradely transported fluorescent dyes. Fast blue and nuclear yellow were injected in the left frontal (areas 4 and 6) and right posterior parietal (area 5) cortices, respectively. These injections led to the retrograde labeling, in the right frontal cortex, of callosal neurons projecting homotopically and association neurons projecting to ipsilateral area 5; in the left superior parietal lobule, of callosal neurons projecting to contralateral area 5 and association neurons projecting to the ipsilateral frontal lobe. In both frontal and parietal cortices, callosal and association neurons were located in layers III and V-VI; a few neurons were also found in layer II. The contribution of layers V-VI to the callosum was significantly higher in areas 4 and 6 than in area 5. Only a small number of neurons (less than 1%) were double labeled. Spectral analyses were used to characterize the spatial periodicities of the distributions of callosal and association neurons. In areas 4, 6, and 5, both association and callosal spectra were dominated by a strong elevation in the range of low spatial frequencies, corresponding to periodicities in cell density with a peak-to-peak distance of about 8 mm. This indicated an arrangement of these corticocortical cells in the form of bands. The latter displayed various shapes and orientations and were composed of more discrete assemblies of cell clusters of about 400-1000 microns width. Their presence was revealed in the power spectra by a small elevation in the range of high spatial frequencies. The coherency analysis assessed the degree of linear relationships for each spatial frequency, and therefore the degree of similarity, between callosal and association cell distributions, together with their phase relations. Little coherency was found in areas 4 and 6 between bands of callosal and association neurons, which suggests that the 2 cell populations are differently and independently distributed in the tangential domain, with no simple phase relations. The overall mean coherency was higher in area 5 than in the frontal cortex: callosal and association bands were more similar in shape, with more extensive zones of overlap. These data indicate that callosal and association neurons share common principles of spatial organization despite the great regional variability of their interrelations in the tangential cortical domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals