On the neurons with dendrites intermingling with the fibers of the human corpus callosum: a Golgi picture

Golgi preparations of the anterior part of the truncus of the corpus callosum from 11 adult human brains were investigated. The vertical plane of section was situated symmetrically between the frontal and sagittal plane. The use of this oblique plane of section enabled easy identification of the neurons with dendrites intermingling with transcallosal fibers, what was not possible in standard frontal sections. 2 types of such neurons (with features of other interstitial neurons) were described: fusiform and multipolar. Both types of neurons were more frequently impregnated in areas adjacent to induseum griseum, cingular cortex, and in the depth of the callosal sulcus. Multipolar neurons were also present in the central core and in ventral parts of the corpus callosum, but fusiform ones were not present in ventral parts of the corpus callosum truncus. The dentrites of both types of neurons usually were perpendicular to, sometimes also parallel to transcallosal fibers. The impregnation of these neurons in groups and pairs suggest their integrative role, and their planar orientation in mentioned oblique plane corresponds to oblique direction of transcallosal cingulostriatal decussating fibers.     

The relationship of callosal anatomy to paw preference in dogs

Previous studies have described the paw preference and asymmetry in dog brains, based on experimental studies. The purpose of the present study is to investigate a possible association between callosal anatomy and paw preference in dogs. The midsagittal area of the dog corpus callosum was measured in its entirety and in six subdivisions in a sample of 21 brains obtained from 9 male and 12 female mongrel dogs which had paw preference testing. The present study showed significant paw differences in dog corpus callosum. A posterior segment of the callosum, the isthmus, was significantly larger in the right pawedness than the left.     

Transient cellular structures in developing corpus callosum of the human brain

The corpus callosum connects two cerebral hemispheres as the most voluminous fiber system in the human brain. The developing callosal fibers originate from immature pyramidal neurons, grow through complex pathways and cross the midline using different substrates in transient fetal structures. We analyzed cellular structures in the human corpus callosum on postmortem brains from the age of 18 weeks post conception to adult, using glial fibrillary acidic protein, neuron-specific nuclear protein, and chondroitin sulphate immunocytochemistry. We found the presence of transient cellular structures, callosal septa, which divide major fiber bundles and ventrally merge with subcallosal zone forming grooves for callosal axons. The callosal septa are composed of glial fibrillary acidic protein reactive meshwork, neurones and the chondroitin sulphate immunoreactive extracellular matrix. The developmental window of prominence of the callosal septa is between 18-34 weeks post conception which corresponds to the period of most intensive growth of callosal axons in human. During the early postnatal period the callosal septa become thinner and shorter, lose their neuronal and chondroitin sulphate content. In conclusion, transient expression of neuronal, glial and extracellular, growing substrate in the callosal septa, as septa itself, indicates their role in guidance during intensive growth of callosal fibers in the human brain. These findings shed some light on the complex morphogenetic events during the growth of the corpus callosum and represent normative parameters necessary for studies of structural plasticity after perinatal lesions.     

A function of the corpus callosum in the Siamese cat

Recordings were made from 180 single cells, or cell clusters, in the Clare-Bishop area of two Siamese cats. In one cat, the corpus callosum had been sectioned prior to recording and all cells were driven by the contralateral eye exclusively. In the other recordings were made before and after callosal section. Before callosal section, most cells were binocularly driven but dominated by the contralateral eye. There were striking examples of binocular interaction and some cells could only be activated by simultaneous binocular stimulation. After callosal section, cells were driven by the contralateral eye only. The same experiment performed in a normal cat revealed no change in binocularity following section of the corpus callosum. We conclude that one of the functions of the corpus callosum in the Siamese cat is to generate binocular neurons.     

Size and position of the human adhaesio interthalamica

In 50 human brains, we investigated the size of the adhaesio interthalamica, length of CA-CP line, position of the centre of adhaesio interthalamica, and the distance between the corpus callosum and adhaesio interthalamica. Interthalamic adhesion was absent in 11 brains (22%) and was duplicated in 1 brain. In all 50 brains, length of the intercommissural line (CA-CP) had a mean value of 2.56 cm, in brains with the interthalamic adhesion 2.48 cm, and 2.56 cm in brains without it. t-test for this difference showed no significant result for a probability of 0.05 (t = 1.95). Midsagittal section area of adhaesio interthalamica had a mean value of 13.1 mm2 (min = 1.5 mm2; max = 34 mm2). There is no correlation between the length of CA-CP line and the size of the midsagittal section area of adhaesio interthalamica (the correlation coefficient was 0.06). The centre of adhaesio interthalamica was most often situated above the CA-CP line and around the perpendicular line through its middle portion. The distance between the corpus callosum and interthalamic adhesion, measured in standardized system of CA-CP line, had a mean value 1.4 cm (min = 0.7 cm; max = 2.3 cm). Our results confirm the opinions that the presence of size of the interthalamic adhaesion depends not directly on the size of the corresponding brain (diencephalon).     

Changes of the corpus callosum in children who suffered perinatal injury of the periventricular crossroads of pathways

There is a high incidence of periventricular leukomalacia, caused by hypoxia-ischemia, in preterm infants. These lesions damage the periventricular crossroads of commissural, projection and associative pathways, which are in a close topographical relationship with the lateral ventricles. We explored to what extent abnormalities of echogenicity of the periventricular crossroads correlate with changes in size of the corpus callosum. Our study included nine infants (gestation from 26-41 weeks; birth weight between 938-4450 grams) with perinatal brain injury. Periventricular areas, which topographically correspond to the frontal, main and occipital crossroad, were readily visualized by cranial ultrasound scans, performed during the first two weeks after birth. Corpus callosum mediosagittal area measurements were performed using magnetic resonance images, acquired between the first and sixth postnatal month (postmenstrual age 40-49 weeks). We found a statistically significant correlation between the increased echogenicity in the crossroad areas and the decrease of the corpus callosum midsagittal area (p < 0.05). This supports the hypothesis that callosal fibers can be damaged, during growth through the periventricular crossroads of pathways.     

Callosal neurons: monosynaptic connection between them and their descending projections

Antidromic and monosynaptic unit responses to the stimulation of the corpus callosum and the symmetrical cortical area as well as antidromic responses to pyramidal tract and thalamic nuclei stimulation were recorded in the sensorimotor cortex of unanaesthetized rabbits. Out of 182 callosal neurones 13 exhibited transcallosal monosynaptic responses. 8 out of 56 callosal units responded antidromically to pyramidal tract or thalamic stimulation. Thus callosal neurones may be monosynaptically excited by callosal units via the corpus callosum and by the pyramidal tract units. It was also found that a pyramidal tract neurone may send a collateral through the corpus callosum and at the same time have a transcallosal monosynaptic input. The role of monosynaptic transcallosal excitation of callosal neurones is discussed.     

Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization

Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.     

Sex differences in dog corpus callosum.

Human studies reported sex differences in size and shape of the corpus callosum. These observations have been contested. The purpose of the present study is to investigate possible sex differences in the corpus callosum of dogs. The entire brains including the medulla from 12 female and 9 male adult mongrel dogs were removed and weighed. Total and partial area measurements of the callosum were made from photographic tracings of its outline. The callosum was partitioned into 3 regions; anterior half, posterior half, posterior one-fifth. The total corpus callosum, anterior half, posterior half, and posterior fifth or splenium areas were measured. Sex differences were found. The anterior half, the posterior half, the posterior fifth, and the total callosum were significantly greater in absolute area in males than in females.     

Wnt/calcium signaling mediates axon growth and guidance in the developing corpus callosum

It has been shown in vivo that Wnt5a gradients surround the corpus callosum and guide callosal axons after the midline (postcrossing) by Wnt5a-induced repulsion via Ryk receptors. In dissociated cortical cultures we showed that Wnt5a simultaneously promotes axon outgrowth and repulsion by calcium signaling. Here to test the role of Wnt5a/calcium signaling in a complex in vivo environment we used sensorimotor cortical slices containing the developing corpus callosum. Plasmids encoding the cytoplasmic marker DsRed and the genetically encoded calcium indicator GCaMP2 were electroporated into one cortical hemisphere. Postcrossing callosal axons grew 50% faster than pre-crossing axons and higher frequencies of calcium transients in axons and growth cones correlated well with outgrowth. Application of pharmacological inhibitors to the slices showed that signaling pathways involving calcium release through IP3 receptors and calcium entry through TRP channels regulate post-crossing axon outgrowth and guidance. Co-electroporation of Ryk siRNA and DsRed revealed that knock down of the Ryk receptor reduced outgrowth rates of postcrossing but not precrossing axons by 50% and caused axon misrouting. Guidance errors in axons with Ryk knockdown resulted from reduced calcium activity. In the corpus callosum CaMKII inhibition reduced the outgrowth rate of postcrossing (but not precrossing) axons and caused severe guidance errors which resulted from reduced CaMKII-dependent repulsion downstream of Wnt/calcium. We show for the first time that Wnt/Ryk calcium signaling mechanisms regulating axon outgrowth and repulsion in cortical cultures are also essential for the proper growth and guidance of postcrossing callosal axons which involve axon repulsion through CaMKII.     

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development.     

Functional microsurgical partial callosotomy in patients with secondary generalized epilepsies. I. Disruption of bilateral synchrony of spike and wave discharges

Fourteen patients with secondary generalized epilepsy suffering from multiform seizures (MS) not amenable to medication were submitted to partial section of the corpus callosum. In all patients, there was a partial disruption of the previous generalized bilateral synchronous epileptiform discharges (GBSD). The electroencephalographic findings after callosal section are discussed with respect to their implications in furthering our understanding of the mechanisms subserving the organization of GBSD.     

Brain connections: interhemispheric fiber systems and anatomical brain asymmetries in humans.

The present review summarizes some results of a research program oriented to determine the anatomical substrates of interhemispheric communication in humans, as seen in postmortem material. One main finding is a sensible pattern of histological differentiation along the corpus callosum, indicating specific properties of interhemispheric conduction for axonal fibers involved in different brain functions. Callosal regions that connect primary and secondary sensory and motor areas are characterized by a large proportion of fast-conducting, large-diameter fibers, while regions connecting the so-called association areas and prefrontal areas bear a high density of slow-conducting, lightly myelinated and thin fibers. These findings are interpreted in a functional context, suggesting that the fast-conducting fibers connecting sensory and motor areas contribute to fuse the two hemirepresentations in each hemisphere. It has also been determined that an increased callosal area indicates an increased number of callosal fibers, a finding that validates previous morphometric studies done in several laboratories. No sex differences in callosal size, shape, or in callosal fiber composition were found. Finally, an inverse relation was found between the anatomical asymmetries in the size of the Sylvian fissure and the size and number of fibers in specific segments of the corpus callosum. There were sex differences in terms of the particular callosal regions showing a significant correlation with asymmetries, and in terms of the fiber types that were correlated with asymmetries.     

Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study

Background  

The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections.     

A postmortem study of the corpus callosum in the common minke whale (Balaenoptera acutorostrata)

Cetaceans diverged from terrestrial mammals approximately 53 mya and have evolved independently since then. During this time period, they have developed a complex nervous system with many adaptations to the marine environment. This study used stereological methods to estimate the total number and diameter of the myelinated fibers in the corpus callosum of the common minke whale (Balaenoptera acutorostrata) (n= 4). The total number of callosal fibers was estimated to 55.3 × 10⁶ (range: 49.0 × 10⁶–59.1 × 10⁶). Despite large variations of the callosal area (350–950 mm²), there was little variation in total fiber number. The fibers with diameters ranging from 0.822 to 1.14 μm were the most frequent, which is similar to results obtained in the human brain using the same method. There was no systematic distribution of large‐, middle‐, or small‐sized fibers along the rostrocaudal axis of the corpus callosum. This study indicated that the corpus callosum of the common minke whale is small and has few fibers compared to terrestrial mammals.     

Multiple Slits regulate the development of midline glial populations and the corpus callosum

The Slit molecules are chemorepulsive ligands that regulate axon guidance at the midline of both vertebrates and invertebrates. In mammals, there are three Slit genes, but only Slit2 has been studied in any detail with regard to mammalian brain commissure formation. Here, we sought to understand the relative contributions that Slit proteins make to the formation of the largest brain commissure, the corpus callosum. Slit ligands bind Robo receptors, and previous studies have shown that Robo1(-/-) mice have defects in corpus callosum development. However, whether the Slit genes signal exclusively through Robo1 during callosal formation is unclear. To investigate this, we compared the development of the corpus callosum in both Slit2(-/-) and Robo1(-/-) mice using diffusion magnetic resonance imaging. This analysis demonstrated similarities in the phenotypes of these mice, but crucially also highlighted subtle differences, particularly with regard to the guidance of post-crossing axons. Analysis of single mutations in Slit family members revealed corpus callosum defects (but not complete agenesis) in 100% of Slit2(-/-) mice and 30% of Slit3(-/-) mice, whereas 100% of Slit1(-/-); Slit2(-/-) mice displayed complete agenesis of the corpus callosum. These results revealed a role for Slit1 in corpus callosum development, and demonstrated that Slit2 was necessary but not sufficient for midline crossing in vivo. However, co-culture experiments utilising Robo1(-/-) tissue versus Slit2 expressing cell blocks demonstrated that Slit2 was sufficient for the guidance activity mediated by Robo1 in pre-crossing neocortical axons. This suggested that Slit1 and Slit3 might also be involved in regulating other mechanisms that allow the corpus callosum to form, such as the establishment of midline glial populations. Investigation of this revealed defects in the development and dorso-ventral positioning of the indusium griseum glia in multiple Slit mutants. These findings indicate that Slits regulate callosal development via both classical chemorepulsive mechanisms, and via a novel role in mediating the correct positioning of midline glial populations. Finally, our data also indicate that some of the roles of Slit proteins at the midline may be independent of Robo signalling, suggestive of additional receptors regulating Slit signalling during development.     

Tractography of the Spider Monkey (Ateles geoffroyi) Corpus Callosum Using Diffusion Tensor Magnetic Resonance Imaging

The objective of this research was to describe the organization, connectivity and microstructure of the corpus callosum of the spider monkey (Ateles geoffroyi). Non-invasive magnetic resonance imaging and diffusion-tensor imaging were obtained from three subjects using a 3T Philips scanner. We hypothesized that the arrangement of fibers in spider monkeys would be similar to that observed in other non-human primates. A repeated measure (n = 3) of fractional anisotropy values was obtained of each subject and for each callosal subdivision. Measurements of the diffusion properties of corpus callosum fibers exhibited a similar pattern to those reported in the literature for humans and chimpanzees. No statistical difference was reached when comparing this parameter between the different CC regions (p = 0.066). The highest fractional anisotropy values corresponded to regions projecting from the corpus callosum to the posterior cortical association areas, premotor and supplementary motor cortices. The lowest fractional anisotropy corresponded to projections to motor and sensory cortical areas. Analyses indicated that approximately 57% of the fibers projects to the frontal cortex and 43% to the post-central cortex. While this study had a small sample size, the results provided important information concerning the organization of the corpus callosum in spider monkeys.     

Sexual dimorphism of the human corpus callosum from three independent samples: Relative size of the corpus callosum

Three independent autopsy samples of brains without apparent neuropathology were studied to ascertain whether there was sexual dimorphism in the human corpus callosum (CC). Using planimetric measurements on midsagittal brain sections, several morphometric features of the CC were studied: total callosal area, maximum dorsoventral splenial width, the posterior one fifth of the total area of the CC (mostly splenium), and brain weight. Ratio data correcting for brain size were also studied. In all samples, absolute brain size was larger in males, and significantly so. Measurements of splenial dorsoventral width were higher in females than males, but not significantly, except in the Australian sample. Total callosal area was absolutely higher in the Australian female sample than in males, and almost equal in the two American samples, without statistically significant differences. The posterior one-fifth area (splenium) was larger for females in each of the samples. The variables which were corrected for brain size were usually significantly larger in females, although this pattern varied in each sample. The statistical pattern of sexual dimorphism for the human CC differs from that found in most other neural structures, such as the amygdaloid nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these structures are always significantly larger in males. When corrected for brain size, the relative sizes are not significantly larger. The CC is the only structure to show a larger set of relative measures in females. © 1993 Wiley-Liss, Inc.