Terminal Arbors of Callosal Axons Undergo Plastic Changes in Early-Amputated Rats.

Sensory information is processed in specific brain regions, and shared between the cerebral hemispheres by axons that cross the midline through the corpus callosum. However, sensory deprivation usually causes sensory losses and/or functional changes. This is the case of people who suffered limb amputation and show changes of body map organization within the somatosensory cortex (S1) of the deafferented cerebral hemisphere (contralateral to the amputated limb), as well as in the afferented hemisphere (ipsilateral to the amputated limb). Although several studies have approached these functional changes, the possible finer morphological alterations, such as those occurring in callosal axons, still remain unknown. The present work combined histochemistry, single-axon tracing and 3D microscopy to analyze the fine morphological changes that occur in callosal axons of the forepaw representation in early amputated rats. We showed that the forepaw representation in S1 was reduced in the deafferented hemisphere and expanded in the afferented side. Accordingly, after amputation, callosal axons originating from the deafferented cortex undergo an expansion of their terminal arbors with increased number of terminal boutons within the homotopic representation at the afferented cerebral hemisphere. Similar microscale structural changes may underpin the macroscale morphological and functional phenomena that characterize limb amputation in humans.

Structural and functional brain rewiring clarifies preserved interhemispheric transfer in humans born without the corpus callosum.

Why do humans born without the corpus callosum, the major interhemispheric commissure, lack the disconnection syndrome classically described in callosotomized patients? This paradox was discovered by Nobel laureate Roger Sperry in 1968, and has remained unsolved since then. To tackle the hypothesis that alternative neural pathways could explain this puzzle, we investigated patients with callosal dysgenesis using structural and functional neuroimaging, as well as neuropsychological assessments. We identified two anomalous white-matter tracts by deterministic and probabilistic tractography, and provide supporting resting-state functional neuroimaging and neuropsychological evidence for their functional role in preserved interhemispheric transfer of complex tactile information, such as object recognition. These compensatory pathways connect the homotopic posterior parietal cortical areas (Brodmann areas 39 and surroundings) via the posterior and anterior commissures. We propose that anomalous brain circuitry of callosal dysgenesis is determined by long-distance plasticity, a set of hardware changes occurring in the developing brain after pathological interference. So far unknown, these pathological changes somehow divert growing axons away from the dorsal midline, creating alternative tracts through the ventral forebrain and the dorsal midbrain midline, with partial compensatory effects to the interhemispheric transfer of cortical function.

Social isolation leads to mild social recognition impairment and losses in brain cellularity.

Chronic social stress is a significant risk factor for several neuropsychiatric disorders, mainly major depressive disorder (MDD). In this way, patients with clinical depression may display many symptoms, including disrupted social behavior and anxiety. However, like many other psychiatric diseases, MDD has a very complex etiology and pathophysiology. Because social isolation is one of the multiple depression-inducing factors in humans, this study aims to understand better the link between social stress and MDD using an animal model based on social isolation after weaning, which is known to produce social stress in mice. We focused on cellular composition and white matter integrity to establish possible links with the abnormal social behavior that rodents isolated after weaning displayed in the three-chamber social approach and recognition tests. We used the isotropic fractionator method to assess brain cellularity, which allows us to robustly estimate the number of oligodendrocytes and neurons in dissected brain regions. In addition, diffusion tensor imaging (DTI) was employed to analyze white matter microstructure. Results have shown that post-weaning social isolation impairs social recognition and reduces the number of neurons and oligodendrocytes in important brain regions involved in social behavior, such as the anterior neocortex and the olfactory bulb. Despite the limitations of animal models of psychological traits, evidence suggests that behavioral impairments observed in patients might have similar biological underpinnings.

Myelination of Callosal Axons Is Hampered by Early and Late Forelimb Amputation in Rats.

Deafferentation is an important determinant of plastic changes in the CNS, which consists of a loss of inputs from the body periphery or from the CNS itself. Although cortical reorganization has been well documented, white matter plasticity was less explored. Our goal was to investigate microstructural interhemispheric connectivity changes in early and late amputated rats. For that purpose, we employed diffusion-weighted magnetic resonance imaging, as well as Western blotting, immunohistochemistry, and electron microscopy of sections of the white matter tracts to analyze the microstructural changes in the corticospinal tract and in the corpus callosum (CC) sector that contains somatosensory fibers integrating cortical areas representing the forelimbs and compare differences in rats undergoing forelimb amputation as neonates, with those amputated as adults. Results showed that early amputation induced decreased fractional anisotropy values and reduction of total myelin amount in the cerebral peduncle contralateral to the amputation. Both early and late forelimb amputations induced decreased myelination of callosal fibers. While early amputation affected myelination of thinner axons, late amputation disrupted axons of all calibers. Since the CC provides a modulation of inhibition and excitation between the hemispheres, we suggest that the demyelination observed among callosal fibers may misbalance this modulation.

Electrophysiological Correlates of Morphological Neuroplasticity in Human Callosal Dysgenesis.

In search for the functional counterpart of the alternative Probst and sigmoid bundles, considered as morphological evidence of neuroplasticity in callosal dysgenesis, electroencephalographic (EEG) coherence analysis was combined with high resolution and diffusion tensor magnetic resonance imaging. Data of two patients with callosal agenesis, plus two with typical partial dysgenesis with a remnant genu, and one atypical patient with a substantially reduced genu were compared to those of fifteen neurotypic controls. The interhemispheric EEG coherence between homologous nontemporal brain regions corresponded to absence or partial presence of callosal connections. A generalized coherence reduction was observed in complete acallosal patients, as well as coherence preservation in the anterior areas of the two patients with a remnant genu. jThe sigmoid bundles found in three patients with partial dysgenesis correlated with augmented EEG coherence between anterior regions of one hemisphere and posterior regions of the other. These heterologous (crossed) interhemispheric connections were asymmetric in both imaging and EEG patterns, with predominance of the right-anterior-to-left-posterior connections over the mirror ones. The Probst bundles correlated with higher intrahemispheric long-distance coherence in all patients. The significant correlations observed for the delta, theta and alpha bands indicate that these alternative pathways are functional, although the neuropsychological nature of this function is still unknown.