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Journal of Neurophysiology Nov 2011The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a...
The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map.
Topics: Adolescent; Adult; Brain Mapping; Cerebellum; Cerebral Cortex; Efferent Pathways; Functional Laterality; Humans; Magnetic Resonance Imaging; Motor Cortex; Quality Control; Somatosensory Cortex; Visual Cortex; Young Adult
PubMed: 21795627
DOI: 10.1152/jn.00339.2011 -
Nature Communications Apr 2018Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal...
Exosomes are cell-derived nanovesicles (50-150 nm), which mediate intercellular communication, and are candidate therapeutic agents. However, inefficiency of exosomal message transfer, such as mRNA, and lack of methods to create designer exosomes have hampered their development into therapeutic interventions. Here, we report a set of EXOsomal transfer into cells (EXOtic) devices that enable efficient, customizable production of designer exosomes in engineered mammalian cells. These genetically encoded devices in exosome producer cells enhance exosome production, specific mRNA packaging, and delivery of the mRNA into the cytosol of target cells, enabling efficient cell-to-cell communication without the need to concentrate exosomes. Further, engineered producer cells implanted in living mice could consistently deliver cargo mRNA to the brain. Therapeutic catalase mRNA delivery by designer exosomes attenuated neurotoxicity and neuroinflammation in in vitro and in vivo models of Parkinson's disease, indicating the potential usefulness of the EXOtic devices for RNA delivery-based therapeutic applications.
Topics: 3' Untranslated Regions; Animals; Brain; Catalase; Cell Communication; Cell Line, Tumor; Cerebrum; Cytosol; Drug Delivery Systems; Electroporation; Exosomes; Female; Genetic Therapy; HEK293 Cells; HeLa Cells; Humans; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; MicroRNAs; Nanoparticles; Parkinson Disease; RNA, Messenger; Synthetic Biology
PubMed: 29610454
DOI: 10.1038/s41467-018-03733-8 -
Molecular Cell Aug 2020Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to...
Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.
Topics: Adult; Cell Line; Cerebrum; Chromatin; Chromosome Mapping; Enhancer Elements, Genetic; Fetus; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genome, Human; Histones; Humans; Induced Pluripotent Stem Cells; Nerve Tissue Proteins; Neural Stem Cells; Neurodegenerative Diseases; Neurogenesis; Neurons; Promoter Regions, Genetic; Temporal Lobe; Transcription Factors
PubMed: 32592681
DOI: 10.1016/j.molcel.2020.06.007 -
CMAJ : Canadian Medical Association... Jan 2021
Topics: Cerebrum; Computed Tomography Angiography; Defecation; Female; Headache Disorders, Primary; Humans; Middle Aged; Vasoconstriction
PubMed: 33667187
DOI: 10.1503/cmaj.201234-f -
Proceedings of the National Academy of... Jun 2023The human cerebrum consists of a precise and stereotyped arrangement of lobes, primary gyri, and connectivity that underlies human cognition [P. Rakic, , 724-735...
The human cerebrum consists of a precise and stereotyped arrangement of lobes, primary gyri, and connectivity that underlies human cognition [P. Rakic, , 724-735 (2009)]. The development of this arrangement is less clear. Current models explain individual primary gyrification but largely do not account for the global configuration of the cerebral lobes [T. Tallinen, J. Y. Chung, J. S. Biggins, L. Mahadevan, , 12667-12672 (2014) and D. C. Van Essen, , 313-318 (1997)]. The insula, buried in the depths of the Sylvian fissure, is unique in terms of gyral anatomy and size. Here, we quantitatively show that the insula has unique morphology and location in the cerebrum and that these key differences emerge during fetal development. Finally, we identify quantitative differences in developmental migration patterns to the insula that may underlie these differences. We calculated morphologic data in the insula and other lobes in adults (N = 107) and in an in utero fetal brain atlas (N = 81 healthy fetuses). In utero, the insula grows an order of magnitude slower than the other lobes and demonstrates shallower sulci, less curvature, and less surface complexity both in adults and progressively throughout fetal development. Spherical projection analysis demonstrates that the lenticular nuclei obstruct 60 to 70% of radial pathways from the ventricular zone (VZ) to the insula, forcing a curved migration to the insula in contrast to a direct radial pathway. Using fetal diffusion tractography, we identify radial glial fascicles that originate from the VZ and curve the lenticular nuclei to form the insula. These results confirm existing models of radial migration to the cortex and illustrate findings that suggest differential insular and cerebral development, laying the groundwork to understand cerebral malformations and insular function and pathologies.
Topics: Insular Cortex; Diffusion Tensor Imaging; Fetal Development; Humans; Male; Female; Young Adult; Adult
PubMed: 37279278
DOI: 10.1073/pnas.2220200120 -
ENeuro 2022Serotonin (5-HT) participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), but its effects have not been completely clarified. Therefore, we observed the...
Serotonin (5-HT) participates in the pathogenesis of amyotrophic lateral sclerosis (ALS), but its effects have not been completely clarified. Therefore, we observed the distribution features and potential effects of 5-HT in the cerebrum of G93A SOD1 transgenic (TG) and wild-type (WT) mice by fluorescence immunohistochemistry, Western blotting, ELISA, as well as motor function measurements. Both 5-HT and tryptophan hydroxylase-2 (TPH2) were mainly present in the limbic systems of the cerebrum, such as the glomerular layer of the olfactory bulb, nucleus accumbens, cingulate, fimbria of the hippocampus, mediodorsal thalamic nucleus, habenular nucleus, ventromedial hypothalamus nucleus, lateral hypothalamus area, dorsal raphe nucleus, and piriform cortex. TPH2 and 5-HT were expressed in cell bodies in the dorsal raphe nucleus and piriform cortex, while in other regions they were distributed as filaments and clump shapes in axons. The TPH2 distribution in the cerebrum of TG was significantly lower than that in WT in preset, onset, and progression stages. TPH2 expression in the fimbria of the hippocampus, mediodorsal thalamic nucleus, habenular nucleus, ventromedial hypothalamus nucleus and lateral hypothalamus area was increased in the onset stage and decreased in the progression stage, gradually decreased in the cingulate with disease progression and significantly decreased in the glomerular layer of the olfactory bulb and nucleus accumbens in the onset stage in TG. The number of mammalian achaete-scute homolog-1 in the subventricular zone (SVZ) in TG was significantly lower than that in WT, which was correlated with the TPH2 distribution. Double immunofluorescence staining showed that TPH2, mammalian achaete-scute homolog-1 and 5-HT were mainly expressed in neurons but rarely expressed in microglia or astrocytes in the piriform cortex. The relative fluorescence density of TPH2 in the cingulate region was negatively correlated with the disease severity. Our findings suggest that 5-HT plays a protective role in ALS, likely by regulating neural stem cells in the subventricular zone that might be involved in neuron development in the piriform cortex.
Topics: Animals; Mice; Amyotrophic Lateral Sclerosis; Cerebrum; Mice, Transgenic; Serotonin; Superoxide Dismutase-1
PubMed: 36265904
DOI: 10.1523/ENEURO.0001-22.2022 -
NeuroImage Feb 2020This analysis explores the effective connectivity of the cerebellum with the cerebral cortex during the generation of correct sequences of social and non-social events,...
This analysis explores the effective connectivity of the cerebellum with the cerebral cortex during the generation of correct sequences of social and non-social events, using dynamic causal modelling (DCM). Our hypothesis is that during human evolution, the cerebellum's function evolved from a mere coordinator of fluent sequences of motions and actions, to an interpreter of action sequences without overt movements that are important for social understanding. This requires efficient neural communication between the cerebellum and cerebral cortex. In a functional magnetic resonance imaging (fMRI) study, participants generated the correct chronological order of (non-)social events, including stories involving mechanical and social scripts, and true or false beliefs. Across all stories, a DCM analysis of these data revealed, as predicted, bidirectional (closed-loop) connections linking the bilateral posterior cerebellum with the bilateral temporo-parietal junction (TPJ) associated with behavior understanding, and this connectivity pattern was almost entirely significant. There was also a unidirectional connection from the right posterior cerebellum to the precuneus, but no direct connections with the dorsomedial prefrontal cortex (dmPFC). Moreover, all connections emanating from the bilateral posterior cerebellum were negative, indicative of some kind of error signal. Within the cerebral cortex, there were unidirectional connections from the bilateral TPJ to the dmPFC, as well as bidirectional connections between the precuneus and dmPFC, and between the bilateral TPJ. These results confirm that the effective connectivity between the posterior cerebellum and mentalizing areas in the cerebral cortex play a critical role in the understanding and construction of the correct order of social and non-social action sequences.
Topics: Bayes Theorem; Cerebellum; Cerebral Cortex; Female; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Male; Mentalization; Neural Pathways; Parietal Lobe; Prefrontal Cortex; Social Perception; Temporal Lobe
PubMed: 31678499
DOI: 10.1016/j.neuroimage.2019.116326 -
Physics of Life Reviews Dec 2019During the short period of brain development, nature is able to build the only system we know capable of producing cognition, language, creativity, and consciousness.... (Review)
Review
During the short period of brain development, nature is able to build the only system we know capable of producing cognition, language, creativity, and consciousness. The neocortex - the outermost layer of the mammalian cerebrum - appears to be the biological substrate of these abilities. Its development requires not only the precise placement and wiring of billions of cells, but also the implementation of mechanisms to ensure a viable cognition despite sometimes dramatic perturbations. Today, this remarkably complex organisation is thought to be genetically encoded, and further refined by activity-dependent processes. We propose that mechanical morphogenesis - the capacity of homogeneously growing elastic tissue to produce complex shapes - can also play an important role. Out of homogeneous growth, mechanical morphogenesis can induce the segregation of the neocortex into mechanical and geometric modules - the neocortical folds. Through the feedback of physical forces on developing tissue, these modules can influence the differentiation and wiring of the neocortex, having a causal role on neocortical development, and providing adaptable and robust units for its evolution.
Topics: Animals; Biological Evolution; Biomechanical Phenomena; Humans; Mechanical Phenomena; Morphogenesis; Neocortex
PubMed: 30738760
DOI: 10.1016/j.plrev.2019.01.012 -
Fa Yi Xue Za Zhi Aug 2019Objective To explore the relationship between the electrical conductivity (EC) and biochemical indicators of rat cerebrum tissues and postmortem intervals (PMIs)...
Objective To explore the relationship between the electrical conductivity (EC) and biochemical indicators of rat cerebrum tissues and postmortem intervals (PMIs) and discuss the mechanism of applying EC to infer PMI. Methods Forty healthy Sprague-Dawley rats were sacrificed and stored in an environment of about 25 ℃. The whole cerebrum tissues of rats were removed respectively at different PMIs of 0, 1, 2, 3, 4, 5, 6, and 7 d, and then made into homogenized impregnation solution. The EC and related biochemical indicators (potassium, sodium, chloride, calcium, inorganic phosphorus, magnesium, uric acid, urea nitrogen and creatinine) in cerebrum tissue impregnation solution were determined, and the relationships among EC in impregnation solution, related biochemical indicators and PMI were analyzed. Results The EC in cerebrum tissues increased gradually with the extension of PMI, and the content of uric acid, urea nitrogen and inorganic phosphorus in its impregnation solution also increased gradually with the extension of PMI. The correlation of EC, uric acid, urea nitrogen, and inorganic phosphorus with PMI was relatively good ( was 0.95-0.99), and there was a linear correlation between the content change of uric acid, urea nitrogen, inorganic phosphorus and EC ( was 0.97-0.99). The changes of the other 6 kinds of biochemical indicators with the extension of PMI within 7 d after the rats' death were non-significant (>0.05). Conclusion The correlation between EC in cerebrum tissues, uric acid, urea nitrogen, inorganic phosphorus and PMI were relatively good, and combining various indicators can also improve the accuracy of PMI estimation.
Topics: Animals; Cerebrum; Electric Conductivity; Forensic Pathology; Postmortem Changes; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 31532144
DOI: 10.12116/j.issn.1004-5619.2019.04.002 -
Pediatric Radiology Mar 2021Neurosonography is an essential imaging modality for assessing the neonatal brain, particularly as a screening tool to evaluate intracranial hemorrhage, hydrocephalus... (Review)
Review
Neurosonography is an essential imaging modality for assessing the neonatal brain, particularly as a screening tool to evaluate intracranial hemorrhage, hydrocephalus and periventricular leukomalacia. The primary advantages of neurosonography include portability, accessibility and lack of ionizing radiation. Its main limitations are intrinsic operator dependence and the need for an open fontanelle. Neurosonographic imaging acquisition is typically performed by placing a sector transducer over the anterior fontanelle and following sagittal and coronal sweeps. The sensitivity of neurosonography has markedly improved thanks to the adoption of modern imaging equipment, the use of dedicated head probes, and the employment of advanced diagnostic US techniques. These developments have facilitated more descriptive identification of specific cerebral anatomical details, improving understanding of the cerebral anatomy by conventional US. Such knowledge is fundamental for enhanced diagnostic sensitivity and is a key to understanding pathological states. Furthermore, familiarity with normal anatomy is crucial for understanding pathological states. Our primary goal in this review was to supplement these technological developments with a roadmap to the cerebral landscape. We accomplish this by presenting a systematic approach to using routine US for consistent identification of the most crucial cerebral landmarks, reviewing their relationship with adjacent structures, and briefly describing their primary function.
Topics: Brain; Cerebrum; Humans; Hydrocephalus; Infant, Newborn; Leukomalacia, Periventricular
PubMed: 33026469
DOI: 10.1007/s00247-020-04794-y