Bilateral integration of sensory and associative brain processing is achieved by precise connections between homologous regions in the two hemispheres via the corpus callosum. These connections form ...postnatally, and unilateral deprivation of sensory or spontaneous cortical activity during a critical period severely disrupts callosal wiring. However, little is known about how this early activity affects precise circuit formation. Here, using in utero electroporation of reporter genes, optogenetic constructs, and direct disruption of activity in callosal neurons combined with whisker ablations, we show that balanced interhemispheric activity, and not simply intact cortical activity in either hemisphere, is required for functional callosal targeting. Moreover, bilateral ablation of whiskers in symmetric or asymmetric configurations shows that spatially symmetric interhemispheric activity is required for appropriate callosal targeting. Our findings reveal a principle governing axon targeting, where spatially balanced activity between regions is required to establish their appropriate connectivity.
•Callosal wiring defects result when early cortical activity is bilaterally dissimilar•Functional callosal circuits form after bilateral, but not unilateral, whisker removal•Normal callosal wiring requires balanced sensory or endogenous cortical activity•Bilateral spatial symmetry of whisker input is instructive for callosal wiring
The corpus callosum connects neurons between the brain hemispheres, and its development is sensitive to neuronal activity. Suárez et al. find that a spatially symmetric interhemispheric balance of cortical activity is required during development for correct targeting of callosal axons.
The corpus callosum is the largest fibre tract in the brain, connecting the two cerebral hemispheres, and thereby facilitating the integration of motor and sensory information from the two sides of ...the body as well as influencing higher cognition associated with executive function, social interaction and language. Agenesis of the corpus callosum is a common brain malformation that can occur either in isolation or in association with congenital syndromes. Understanding the causes of this condition will help improve our knowledge of the critical brain developmental mechanisms required for wiring the brain and provide potential avenues for therapies for callosal agenesis or related neurodevelopmental disorders. Improved genetic studies combined with mouse models and neuroimaging have rapidly expanded the diverse collection of copy number variations and single gene mutations associated with callosal agenesis. At the same time, advances in our understanding of the developmental mechanisms involved in corpus callosum formation have provided insights into the possible causes of these disorders. This review provides the first comprehensive classification of the clinical and genetic features of syndromes associated with callosal agenesis, and provides a genetic and developmental framework for the interpretation of future research that will guide the next advances in the field.
Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable ...of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.
Background The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack ...of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. Methods Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemar’s test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. Results The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. Conclusions This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.
Axonal connections between the left and right sides of the brain are crucial for bilateral integration of lateralized sensory, motor, and associative functions. Throughout vertebrate species, ...forebrain commissures share a conserved developmental plan, a similar position relative to each other within the brain and similar patterns of connectivity. However, major events in the evolution of the vertebrate brain, such as the expansion of the telencephalon in tetrapods and the origin of the six-layered isocortex in mammals, resulted in the emergence and diversification of new commissural routes. These new interhemispheric connections include the pallial commissure, which appeared in the ancestors of tetrapods and connects the left and right sides of the medial pallium (hippocampus in mammals), and the corpus callosum, which is exclusive to eutherian (placental) mammals and connects both isocortical hemispheres. A comparative analysis of commissural systems in vertebrates reveals that the emergence of new commissural routes may have involved co-option of developmental mechanisms and anatomical substrates of preexistent commissural pathways. One of the embryonic regions of interest for studying these processes is the commissural plate, a portion of the early telencephalic midline that provides molecular specification and a cellular scaffold for the development of commissural axons. Further investigations into these embryonic processes in carefully selected species will provide insights not only into the mechanisms driving commissural evolution, but also regarding more general biological problems such as the role of developmental plasticity in evolutionary change.
Highlights • Callosal malformations are currently categorised almost solely by midline morphology. • Contralateral targeting of callosal axons after midline crossing is poorly understood. • ...Environmental interaction can affect contralateral targeting after midline crossing. • Contralateral callosal targeting can be highly plastic and variable in humans. • Many neuropathologies may involve undiagnosed changes in contralateral targeting.
Agenesis of the corpus callosum (AgCC), a failure to develop the large bundle of fibres that connect the cerebral hemispheres, occurs in 1:4000 individuals. Genetics, animal models and detailed ...structural neuroimaging are now providing insights into the developmental and molecular bases of AgCC. Studies using neuropsychological, electroencephalogram and functional MRI approaches are examining the resulting impairments in emotional and social functioning, and have begun to explore the functional neuroanatomy underlying impaired higher-order cognition. The study of AgCC could provide insight into the integrated cerebral functioning of healthy brains, and may offer a model for understanding certain psychiatric illnesses, such as schizophrenia and autism.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The brain of mammals differs from that of all other vertebrates, in having a six-layered neocortex that is extensively interconnected within and between hemispheres. Interhemispheric connections are ...conveyed through the anterior commissure in egg-laying monotremes and marsupials, whereas eutherians evolved a separate commissural tract, the corpus callosum. Although the pattern of interhemispheric connectivity via the corpus callosum is broadly shared across eutherian species, it is not known whether this pattern arose as a consequence of callosal evolution or instead corresponds to a more ancient feature ofmammalian brain organization. Here we show that, despite cortical axons using an ancestral commissural route, monotremes and marsupials share features of interhemi-spheric connectivity with eutherians that likely predate the origin of the corpus callosum. Based on ex vivo magnetic resonance imaging and tractography, we found that connections through the anterior commissure in both fat-tailed dunnarts (Marsupialia) and duck-billed platypus (Monotremata) are spatially segregated according to cortical area topography. Moreover, cell-resolution retrograde and anterograde interhemispheric circuit mapping in dunnarts revealed several features shared with callosal circuits of eutherians. These include the layered organization of commissural neurons and terminals, a broad map of connections between similar (homotopic) regions of each hemisphere, and regions connected to different areas (heterotopic), including hyperconnected hubs along the medial and lateral borders of the cortex, such as the cingulate/motor cortex and claustrum/insula. We therefore propose that an interhemispheric connectome originated in early mammalian ancestors, predating the evolution of the corpus callosum. Because these features have been conserved throughout mammalian evolution, they likely represent key aspects of neocortical organization.
The anterior commissure is the most ancient of the forebrain interhemispheric connections among all vertebrates. Indeed, it is the predominant pallial commissure in all non-eutherian vertebrates, ...universally subserving basic functions related to olfaction and survival. A key feature of the anterior commissure is its ability to convey connections from diverse brain areas, such as most of the neocortex in non-eutherian mammals, thereby mediating the bilateral integration of diverse functions. Shared developmental mechanisms between the anterior commissure and more evolutionarily recent commissures, such as the corpus callosum in eutherians, have led to the hypothesis that the former may have been a precursor for additional expansion of commissural circuits. However, differences between the formation of the anterior commissure and other telencephalic commissures suggest that independent developmental mechanisms underlie the emergence of these connections in extant species. Here, we review the developmental mechanisms and connectivity of the anterior commissure across evolutionarily distant species, and highlight its potential functional importance in humans, both in the course of normal neurodevelopment, and as a site of plastic axonal rerouting in the absence or damage of other connections.
•The anterior commissure is conserved throughout vertebrate forebrain evolution.•It is comprised of axons from diverse brain areas across different species.•Ontogenetic mechanisms are compared with other forebrain commissures.•Potential for plastic compensation during pathological brain development.
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