Prenatal specification of callosal connections in rhesus monkey

Anatomical tracing and quantitative techniques were used to examine the tempo and pattern of maturation for callosal projection neurons in the monkey prefrontal cortex (PFC) during fetal and postnatal development. Nineteen monkeys were injected with retrograde tracers (fluorescent dyes, horseradish peroxidase conjugated to wheat germ agglutinin [WGA-HRP] or HRP crystals) at various ages between embryonic day 82 (E82) and adulthood. The size of injection sites was varied in fetal, newborn, and adult cases. In adults, labeled neurons were found in greatest density in the homotopic cortex of the opposite hemisphere and considerable numbers were also observed in a constellation of heterotopic areas including the medial and lateral orbital cortex, the dorsomedial convexity, and the pregenual cortex. The majority of labeled neurons were consistently concentrated in the lower half of layer III in all areas. In cases with large injection sites, callosal neurons of layer III formed a continuous and uninterrupted band that extended over the entire lateral surface of the prefrontal cortex spanning both homotopic and heterotopic areas. In contrast, in cases with small injection sites, the labeling of layer III neurons exhibited discontinuities. Between embryonic ages E82 and E89, injections limited to the cortical layers labeled only a small number of neurons in the opposite hemisphere, indicating that few callosal axons have invaded the cortex by this age. However, by E111 comparable injections labeled a large number of callosal neurons and many features of their distribution were adult-like. The number and constellation of cytoarchitectonic areas that were labeled in the frontal cortex of the opposite hemisphere were the same as in adults and the majority of callosal neurons were found in supragranular layer III. Finally, in fetal animals beyond E111, labeled neurons extended as a nearly unbroken band over a wide expanse of the dorsolateral PFC, resembling the pattern seen in adult monkeys with large injections. The conclusion we draw from these results, together with our earlier findings (Schwartz and Goldman-Rakic: Nature 299:154, 1982), is that callosal neurons whose axons enter the cortical layers of the primate prefrontal cortex achieve their mature laminar and areal distribution prior to birth and do so largely by cumulative processes.     

Variability in the distribution of callosal projection neurons in the adult rat parietal cortex

Previous reports have shown that the barrel field area of the parietal cortex of the adult rat contains relatively few callosal projection neurons, even though callosal projection neurons are abundant in this cortical region in the neonatal rat. Furthermore, it has been shown that many of the callosal neurons which seem to disappear as the animal matures do not die, but project to ipsilateral cortical areas. These findings rely on the ability of retrograde transport techniques which utilize injections of horseradish peroxidase (HRP) or of fluorescent dyes into one hemisphere. We now show that several technical modifications of the HRP technique yield a wider distribution of HRP-containing neurons in the contralateral barrel field area of the adult rat than previously reported. These include implants of HRP pellets into transected axons of the corpus callosum, the addition of DMSO and nonidet P40 to Sigma VI HRP, wheat germ agglutinin HRP and the use of tetramethyl benzidine as the chromogen in the reaction procedure. Our findings have implications for transport studies in general and for the development of the cortical barrel field in particular.     

Axons of callosal neurons bifurcate transiently at the white matter before consolidating an interhemispheric projection

The main alternative output routes of adult cortical axons are the internal capsule and the corpus callosum. How do callosal axons choose their trajectories? We hypothesized that bifurcation followed by elimination of one branch is a developmental strategy for accomplishing this aim. Using embryonic and postnatal mice, we labelled cortical projecting neurons and quantified their axonal bifurcations in correlation with the mediolateral position of their somata. Bifurcating axons were numerous in the younger brains but declined during further development. Most bifurcating axons pertained to neurons located in the dorsolateral cortex. Moreover, callosal neurons bifurcate more often than subcortically projecting cells. We then quantified bifurcations formed by dissociated green fluorescent cells plated onto cortical slices. Cells grown over dorsolateral cortex bifurcated more often than those grown over medial cortex, irrespective of their positional origin in the donor. Removal of intermediate targets from the slices prevented bifurcation. We concluded that transient bifurcation and elimination of the lateral branch is a strategy employed by developing callosal axons in search of their targets. As cell body position and intermediate targets determine axon behaviour, we suggest that bifurcations are regulated by cues expressed in the environment.     

The distribution of the callosal projection to the occipital visual cortex in rats and mice

The principal finding in this study is that the callosal projection to the occipital cortex in rats and mice follows a complex and highly reproducible pattern which has not previously been described in detail. In some regions, the callosal projection is associated with well defined cytoarchitectonic boundaries such as the border between areas 17 and 18a. However, extrastriate cortex lateral to area 17 receives callosal inputs which are not related to previously defined cytoarchitectonic boundaries. Following intraocular injections of [³H]fucose, transneuronal label occupies area 17 and mainly the posterior part of area 18a. A region in posterolateral area 18a which is ‘subdivided’ into callosal and sparsely callosal regions appears to receive an input from the lateral geniculate nucleus, based on transneuronal autoradiography. Comparison of the distribution of callosal axons and transneuronal label suggests that regions of murid cortex similar to areas 18, 19 and lateral suprasylvian cortex in cats may be located posteriorly in area 18a.     

The relation of corpus callosum connections to architectonic fields and body surface maps in sensorimotor cortex of new and old world monkeys

Corpus callosum connections of parietal and motor cortex were studied in New World owl monkeys (Aotus trivirgatus)and Old World macaque monkeys (Macaca fascicnlaris) after multiple injections of ³H-proline and horseradish peroxidase, HRP, into one cerebral hemisphere, and extensive microelectrode mapping of architectonic Areas 3b, 1, and 2 of the other hemisphere. Results were obtained both from parasagittal brain sections cut orthogonal to the brain surface and from sections from flattened brains cut parallel to the brain surface. Cortical fields varied in density of callosal connections, and the density of connections varied according to body part within sensory representations. Thus, Area 3b had few, Area 1 had more, and Area 2 had relatively dense callosal connections. Within each of these fields, connections were much less dense for the representations of the glabrous hand and foot and much more dense for the representations of the face and trunk. For the representation of the hand, retrogradely labeled cells were extremely sparse in Area 3b, moderately sparse in Area 1, and moderate in Area 2. There were less dense callosal connections in the hand representations of Areas 3b, 1, and 2 in macaque as compared to owl monkeys. Label in posterior parietal cortex was uneven with zones of extremely dense connections. A large region of very dense callosal connections was noted in motor cortex just medial to the probable location of the hand representation. In all regions, callosally projecting cells appeared to be more broadly distributed than callosal terminations. In no region was the discontinuous arrangement of callosal connections obviously organized into an extensive pattern of mediolateral or rostrocaudal bands or strips.     

Widespread callosal connections in infragranular visual cortex of the rat

Following multiple injections of HRP into the posterior cortex of one hemisphere of adult rats, dense and overlapping distributions of retrogradely labeled cells and anterogradely labeled terminations are observed throughout the depth of the cortex in the region of the border between the lateral portion of area 17 and area 18 in the opposite hemisphere. In contrast to previous studies of the visual callosal pathway, we also find large numbers of labeled callosal cells extending throughout areas 17 and 18 in cortical layers Vc and VIa.     

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.     

Synapses of extrinsic and intrinsic origin made by callosal projection neurons in mouse visual cortex

Neurons in areas 17/18a and 17/18b of mouse cerebral cortex were labeled by the retrograde transport of horseradish peroxidase (HRP) transported from severed callosal axons in the contralateral hemisphere. Terminals of the local axon collaterals of labeled neurons (intrinsic terminals) were identified in the border regions of area 17 with areas 18a and 18b, and their distribution and synaptic connectivity were determined. Also examined were the synaptic connections of extrinsic callosal axon terminals labeled by lesion-induced degeneration consequent to the severing of callosal fibers. A postlesion survival time of 3 days was chosen because by this time the extrinsic terminals were all degenerating, whereas the intrinsic terminals were labeled by horseradish peroxidase. Both intrinsic and extrinsic callosal axon terminals occurred in all layers of the cortex where, with rare exception, they formed asymmetrical synapses. Layers II and III contained the highest concentrations of intrinsic and extrinsic callosal axon terminals. Analyses of serial thin sections through layers II and III in both areas 17/18a and 17/18b yielded similar results: 97% of the intrinsic (1,412 total sample) and of the extrinsic (414 total sample) callosal axon terminals synapsed onto dendritic spines, likely those of pyramidal neurons; the remainder synapsed onto dendritic shafts of both spiny and nonspiny neurons. Thus, the synaptic output patterns of intrinsic vs. extrinsic callosal axon terminals are strikingly similar. Moreover, the high proportion of axospinous synapses formed by both types of terminal (97%) contrasts with the proportion of asymmetrical axospinous synapses that occurs in the surrounding neuropil where about 64% of the asymmetrical synapses are onto spines. This result is in accord with previous quantitative studies of the synaptic connectivities of callosal projection neurons in mouse somatosensory cortex, and lends additional weight to the hypothesis that axonal pathways are highly selective for the types of elements with which they synapse.     

Connectional analysis of the ipsilateral and contralateral afferent neurons of the superior temporal region in the rhesus monkey

The interhemispheric and ipsilateral afferents of the superior temporal region (STR) were investigated with the aid of fluorescent retrograde tracers (Diamidino Yellow and Fast Blue). Different tracers were injected in selected cortical areas of the STR of each hemisphere of four rhesus monkeys. The results show that the interhemispheric afferents originate not only from the homotopic but also from heterotopic areas. The heterotopic areas giving rise to interhemispheric projections correspond to cortical areas of the origin of the ipsilateral projections. Although there is considerable overlap of labeled neurons of both afferent systems, only occasional double-labeled neurons are found. Whereas the laminar patterns of ipsilateral neurons of origin vary considerably, the interhemispheric projection neurons are located mainly in cortical layer III. This study provides additional information about the ipsilateral connectional organization of the superior temporal region. That is, the primary auditory area receives projections not only from adjacent lateral and medial cortical regions but also from adjoining rostral and caudal cortical regions. Thus, the highly differentiated primary auditory cortical area receives strong projections from the surrounding less-differentiated cortical regions. This connectional pattern is discussed from the perspective of the growth ring concept of cortical development.     

Synapses made by axons of callosal projection neurons in mouse somatosensory cortex: emphasis on intrinsic connections

This is one of a series of papers aimed at identifying the synaptic output patterns of the local and distant projections of subgroups of pyramidal neurons. The subgroups are defined by the target site to which their main axon projects. Pyramidal neurons in areas 1 and 40 of mouse cerebral cortex were labeled by the retrograde transport of horseradish peroxidase (HRP) transported from severed callosal axons in the contralateral hemisphere. Terminals of the local axon collaterals of these neurons ("intrinsic" terminals) were identified in somatosensory areas 1 and 40, and their distribution and synaptic connectivity were examined. Also examined were the synaptic connections of "extrinsic" callosal axon terminals labeled by lesion induced degeneration consequent to the severing of callosal fibers. A post-lesion survival time of 3 days was chosen because by this time the extrinsic terminals were all degenerating, whereas the intrinsic terminals were labeled by HRP. Both intrinsic and extrinsic callosal axon terminals occurred in all layers of the cortex where they formed only asymmetrical synapses. Layers II and III contained the highest concentrations of both types of callosal axon terminal. Analyses of serial thin sections through layers II and III in both areas 1 and 40 yielded similar results: 97% of the extrinsic (277 total sample) and of the intrinsic (1215 total sample) callosal axon terminals synapsed onto dendritic spines, likely those of pyramidal neurons; the remainder synapsed onto dendritic shafts of both spiny and nonspiny neurons. Thus the synaptic output patterns of intrinsic vs. extrinsic callosal axon terminals are strikingly similar. Moreover, the high proportion of axospinous synapses formed by both types of terminal contrasts with the proportion of asymmetrical, axospinous synapses that occur in the surrounding neuropil where only about 80% of the asymmetrical synapses are onto spines. This result is in accord with previous quantitative studies of the synaptic connectivities of both extrinsic and intrinsic axonal pathways in the cortex (White and Keller, 1989: Cortical Circuits; Boston: Birkhauser): in all instances, axonal pathways are highly selective for the types of elements with which they synapse.     

Comparison of the distribution of parvalbumin-immunoreactive and other synapses onto the somata of callosal projection neurons in mouse visual and somatosensory cortex

The distribution of synapses made by parvalbumin-immunoreactive (pv-ir) and nonimmunoreactive terminals was determined for the cell bodies of callosal projection neurons in the somatosensory and visual areas of mouse cerebral cortex. Callosal neurons were labeled by the retrograde transport of horseradish peroxidase applied to the contralateral hemisphere. The surface areas of somata belonging to callosal cells in somatosensory cortex ranged from 230 to 243 μm² in size and received roughly one-third of their synapses from pv-ir terminals. Visual cortex, in contrast, contained two populations of callosal cell bodies: relatively large ones ranging in size from 255 to 279 μm² that received 3–9% of their synapses from pv-ir terminals and smaller cell bodies that both in size (232–237 μm²) and in the proportion of synapses received from pv-ir terminals resemble the callosal cells examined in somatosensory cortex. That different functional areas of the cortex have populations of callosal cells similar in size, and displaying similar patterns of somatic synapses, supports the notion that a common plan of synaptic connectivity characterizes different functional areas. Results in visual cortex indicate that functional areas contain, in addition, area-specific patterns of synapses. J. Comp. Neurol. 379:198–210, 1997. © 1997 Wiley-Liss, Inc.     

Age-related changes in the distribution of visual callosal neurons following monocular enucleation in the rat

The distribution of visual callosal neurons was identified in tangential sections from flattened hemispheres of normal rats and animals unilaterally enucleated at various postnatal ages with the retrogradely transported fluorescent label, Fast Blue. Following enucleation on or after postnatal day 10, callosal neurons along the 17/18a border appear adult-like in their configuration. Enucleation prior to this age stabilizes callosal development in the hemisphere contralateral to the enucleated eye.     

Topography of occipital lobe commissural connections in the rhesus monkey

The organization of occipital lobe commissural connections is re-examined in the rhesus monkey by the autoradiographic technique. A general topographic order was observed in the splenium. Fibers from area 18 occupy its most caudal and ventral subdivision, while those from different parts of area 19 surround the area 18 zone rostrally and dorsally. Results also indicate, however, divergent trajectories within each compartment, as well as significant overlap at their borders.     

Interhemispheric connections of cortical sensory areas in tree shrews

Interhemispheric connections were studied in tree shrews (Tupaia belangeri) after multiple injections of horseradish peroxidase or horseradish peroxidase conjugated to wheat germ agglutinin into the cortex of one cerebral hemisphere. After an appropriate survival period, the areal pattern of connections was revealed by flattening the other hemisphere, cutting sections parallel to the cortical surface, and staining with tetramethylbenzidine. Architectonic boundaries were identified by using sections stained for myelinated fibers. Labeled cells and axon terminations formed largely overlapping distributions that covaried in density, although labeled cells appeared to be more evenly distributed than labeled terminations. Connections were concentrated along the border of area 17 (V-I) with area 18 (V-II). However, connections also extended as far as 2 mm into area 17 to include cortex representing parts of the visual field 10° or more from the zero vertical meridian. Clusters of dense connections spanned the width of area 18, where they alternated with regions of fewer connections. These clusters roughly corresponded in location to regions with heavier myelination. In the visually responsive temporal cortex, connections were also unevenly distributed. The organization of most of this cortex is not understood, but one subdivision, the temporal dorsal area (TD), has been identified on the basis of reciprocal connections with area 17. The central part of the TD had few interhemispheric connections, while most of the outer border had dense connections. The auditory cortex had dense and patchy connections throughout. The pattern in the primary somatosensory cortex (S-I) varied according to the representation of body parts, so that the cortex related to the forepaw had sparse connections, while connections were dense but uneven over much of the representation of the face, nose, and mouth. A focus of connections was found at the border of the forepaw and face representations, where the myelination of S-I cortex is interrupted. Dense, uneven connections also characterized the second somatosensory area, S-II. The motor cortex was densely connected, with only slightly fewer terminations rostral to the forepaw region of S-I. Other parts of frontal cortex had dense connections, The distribution of cortical connections varied with depth for at least some areas, so that clusters of cells and terminations were found in supragranular layers in S-I, S-II, and TD, while infragranular labeled cells were more evenly distributed. The results indicate that interhemispheric connections in tree shrews are widely distributed and include large portions of primary sensory fields, and that the primary somatic and visual areas have more interhemispheric connections than their homologues in higher primates. The local unevenness of the connections suggests that functions are unevenly distributed within cortical areas. Because visual and somatic areas representing the contralateral visual hemifield or body surface receive callosal inputs, many of these connections are not reflected in the excitatory receptive fields of cortical neurons.     

Interhemispheric pathways of the hippocampal formation, presubiculum, and entorhinal and posterior parahippocampal cortices in the rhesus monkey: the structure and organization of the hippocampal commissures

The interhemispheric pathways originating in the hippocampal formation, presubiculum, and entorhinal and posterior parahippocampal cortices and coursing through the fornix system were investigated by autoradiographic tracing in 29 rhesus monkeys (Macaca mulatta). The results revealed that crossing fibers are segregated into three contiguous systems. A ventral hippocampal commissure lies at the transition between the body and anterior columns of the fornix in the vicinity of the subfornical organ and the interventricular foramina of Monro; it is formed by axons arising in the most anterior (uncal and genual) subdivisions of the hippocampal formation. A dorsal hippocampal commissure lies inferior to the posterior end of the body of the corpus callosum; it is formed by axons arising in the presubiculum and entorhinal cortex of the anterior parahippocampal gyrus and the proisocortical and neocortical subdivisions of the posterior parahippocampal gyrus but not in the hippocampal formation. A hippocampal decussation lies between the ventral hippocampal commissure and dorsal hippocampal commissure; it is formed by axons arising in the body of the hippocampal formation. In contrast to the fibers of the ventral hippocampal commissure and dorsal hippocampal commissure, which terminate in contralateral cortical areas, these decussating fibers terminate in the contralateral septum. Thus, the ventral hippocampal commissure and dorsal hippocampal commissure of the rhesus monkey appear to be homologous to similarly designated structures in other mammals. To the extent that these observations also apply to the interhemispheric fibers of the human hippocampal formation and parahippocampal areas, their possible preservation must be considered when interpreting the effect of callosal transection on seizures and the results of "split-brain" studies, since callosal transection may fail to sever the hippocampal commissures in their entirety.     

Tangential organization of callosal connectivity in the cat's visual cortex

Cells and/or terminals of corticocortical pathways in mammalian visual cortex often have a discontinuous distribution across the surface of the cortex. A modular organization of cortical function has been shown to underlie the tangential segregation of many inputs and outputs. Here, we present evidence that the callosal pathway in the visual cortex of the cat follows these general principles. Large injections of wheat germ agglutinin-horseradish peroxidase or biotinylated dextran amine were made in areas 17 and 18, and callosal labeling was analyzed in tangential sections. The band of callosal cells and terminals straddling the border of areas 17 and 18 was not uniform but varied in density in a complicated fashion. Fluctuations in density of callosal connections became more clear 2–3 mm lateral or medial to the 17/18 border, as the callosal labeling became less dense. Here, regular fluctuations with a periodicity of about 1 mm in area 17, and slightly greater than 1 mm in area 18 were apparent. Cytochrome oxidase staining in areas 17 and 18 showed a pattern of dense blobs with the same spacing as the callosal labeling in these areas, and the blobs were found to align with the patches of callosal labeling. Larger, more irregularly spaced stripes of callosal labeling extended from the lateral part of area 18 across area 19 and into more lateral visual areas. These results suggest that the callosal pathway in the cat's visual cortex has a patchy distribution similar to many ipsilateral corticocortical projections, and that the columnar system marked by cytochrome oxidase is important for the organization of (interhemispheric) corticocortical connectivity in cats. © 1994 Wiley-Liss, Inc.     

Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients

To verify whether the activation of the posterior parietal and parietal opercular cortices to tactile stimulation of the ipsilateral hand is mediated by the corpus callosum, a functional magnetic resonance imaging (fMRI, 1.0 tesla) study was performed in 12 control and 12 callosotomized subjects (three with total and nine with partial resection). Eleven patients were also submitted to the tactile naming test. In all subjects, unilateral tactile stimulation provoked a signal increase temporally correlated with the stimulus in three cortical regions of the contralateral hemisphere. One corresponded to the first somatosensory area, the second was in the posterior parietal cortex, and the third in the parietal opercular cortex. In controls, activation was also observed in the ipsilateral posterior parietal and parietal opercular cortices, in regions anatomically corresponding to those activated contralaterally. In callosotomized subjects, activation in the ipsilateral hemisphere was observed only in two patients with splenium and posterior body intact. These two patients and another four with the entire splenium and variable portions of the posterior body unsectioned named objects explored with the right and left hand without errors. This ability was impaired in the other patients. The present physiological and anatomical data indicate that in humans activation of the posterior parietal and parietal opercular cortices in the hemisphere ipsilateral to the stimulated hand is mediated by the corpus callosum, and that the commissural fibres involved probably cross the midline in the posterior third of its body.     

Distribution of GAD-immunoreactive neurons in the first (SI) and second (SII) somatosensory cortex of the monkey

The distribution of neurons immunoreactive for glutamic acid decar☐ylase (GAD), the synthesizing enzyme of γ-aminobutyric acid (GABA), was examined in the first (SI) and second (SII) somatosensory cortex of monkeys. GAD-like immunoreactive (GAD- LI) somata and puncta were present in all layers of SI and SII. All GAD-LI somata were identified as non-pyramidal neurons and were most numerous in layer IV of SI and in layer II of SII. Layer IV of SI also contained the highest density of GAD-LI puncta. In SII, GAD-LI puncta were distributed more homogeneously and did not show a dense band of labelled puncta in layer IV. The major and minor diameters of GAD-LI somata in SII ranged from 6.9 to 26.2 μm and from 6.2 to 19.0 μm, respectively. The major diameters of GAD-LI somata in SII were significantly smaller than those in SI in layers I, III and IV. Differences between the distributions of GAD-LI puncta and somata in SI and SII may be accounted for by differences in the number and/or distribution of different types of GABAergic neurons. Functional differences of neurons in SI and SII may be related to the differences in GABAergic inhibitory mechanisms and reflected in the distribution of GABAergic neurons.     

Interhemispheric connections of somatosensory cortex in the flying fox

The interhemispheric connections of somatosensory cortex in the gray-headed flying fox (Pteropus poliocephalus) were examined. Injections of anatomical tracers were placed into five electrophysiologically identified somatosensory areas: the primary somatosensory area (SI or area 3b), the anterior parietal areas 3a and 1/2, and the lateral somatosensory areas SII (the secondary somatosensory area) and PV (pairetal ventral area). In two animals, the hemisphere opposite to that containing the injection sites was explored electrophysiologically to allow the details of the topography of interconnections to be assessed. Examination of the areal distribution of labeled cell bodies and/or axon terminals in cortex sectioned tangential to the pial surface revealed several consistent findings. First, the density of connections varied as a function of the body part representation injected. For example, the area 3b representation of the trunk and structures of the face are more densely interconnected than the representation of distal body parts (e.g., digit 1, D1). Second, callosal connections appear to be both matched and mismatched to the body part representations injected in the opposite hemisphere. For example, an injection of retrograde tracer into the trunk representation of area 3b revealed connections from the trunk representation in the opposite hemisphere, as well as from shoulder and forelimb/wing representations. Third, the same body part is differentially connected in different fields via the corpus callosum. For example, the D1 representation in area 3b in one hemisphere had no connections with the area 3b D1 representation in the opposite hemisphere, whereas the D1 representation in area 1/2 had relatively dense reciprocal connections with area 1/2 in the opposite hemisphere. Finally, there are callosal projections to fields other than the homotopic, contralateral field. For example, the D1 representation in area 1/2 projects to contralateral area 1/2, and also to area 3b and SII. J. Comp. Neurol. 402:538–559, 1998. © 1998 Wiley-Liss, Inc.     

Cytological and quantitative characteristics of four cerebral commissures in the rhesus monkey

The number, types, and distribution of distinct classes of axons and glia in four cerebral commissures of the adult rhesus monkey (Macaca mulatta) were determined using electron microscopic and immunocytochemical methods. The two neocortical commissures, the corpus callosum, and the anterior commissure contain small but cytologically distinct archicortical components: the hippocampal commissure, which lies ventral to the splenium of the corpus callosum, and the basal telencephalic commissure, which forms a small crescent at the anterior margin of the anterior commissure. Each archicortical pathway is delineated from the adjacent neocortical commissure by a glial capsule. The glia cells that form this border are immunoreactive with antisera directed against glial fibrillary acidic protein (GFAP) and issue long processes that form numerous desmosomal junctions with one another. Braids of these glial processes envelop axonal fascicles within the archicortical commissures. In contrast, the GFAP-positive cells of the corpus callosum and anterior commissure are randomly distributed cells with relatively short stellate processes that do not form boundaries around axon fascicles. Quantitative electron microscopic analysis reveals that approximately 60 million axons connect the two cerebral hemispheres: the corpus callosum contains 56.0 million +/- 3.8 million axons (n = 8), the anterior commissure contains 3.15 million +/- 0.24 million axons (n = 8), the hippocampal commissure has 237,000 axons +/- 31,000 (n = 6), and the basal telencephalic commissure has 193,000 axons +/- 28,000 (n = 5). The number of axons is not directly proportional to the cross-sectional area in any of the commissures because of variation in axonal composition. On the basis of an estimate of approximately 3 billion neurons in the monkey cortex (Shariff, '53), we estimate that between 2 and 3% of all cortical neurons project to the opposite cerebral hemisphere. Subregions of the corpus callosum as well as each of the other commissures consist of characteristic subsets of five classes of axons and contain different proportions of myelinated to unmyelinated fibers. The largest myelinated axons and the smallest proportion of unmyelinated axons (approximately 6%) are found in regions of the corpus callosum that carry projections from primary sensory cortices, whereas the smallest myelinated axons and largest proportion of unmyelinated axons (approximately 30%) are found in regions of the corpus callosum that carry projections from association cortices. Axon composition in the anterior commissure is uniform and resembles that of callosal sectors that contain association projections.(ABSTRACT TRUNCATED AT 400 WORDS)