scholarly journals Cellular Anatomy of the Mouse Primary Motor Cortex

2020 ◽  
Author(s):  
Rodrigo Muñoz-Castañeda ◽  
Brian Zingg ◽  
Katherine S. Matho ◽  
Quanxin Wang ◽  
Xiaoyin Chen ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Projection Neuron ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Integrated Analysis ◽  
Cell Type ◽  
Structural Framework ◽  
Cellular Resolution ◽  
Cortical Laminar

AbstractAn essential step toward understanding brain function is to establish a cellular-resolution structural framework upon which multi-scale and multi-modal information spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, through a collaborative effort from the Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based description of one brain structure - the primary motor cortex upper limb area (MOp-ul) of the mouse. Applying state-of-the-art labeling, imaging, computational, and neuroinformatics tools, we delineated the MOp-ul within the Mouse Brain 3D Common Coordinate Framework (CCF). We defined over two dozen MOp-ul projection neuron (PN) types by their anterograde targets; the spatial distribution of their somata defines 11 cortical sublayers, a significant refinement of the classic notion of cortical laminar organization. We further combine multiple complementary tracing methods (classic tract tracing, cell type-based anterograde, retrograde, and transsynaptic viral tracing, high-throughput BARseq, and complete single cell reconstruction) to systematically chart cell type-based MOp input-output streams. As PNs link distant brain regions at synapses as well as host cellular gene expression, our construction of a PN type resolution MOp-ul wiring diagram will facilitate an integrated analysis of motor control circuitry across the molecular, cellular, and systems levels. This work further provides a roadmap towards a cellular resolution description of mammalian brain architecture.

scholarly journals Cellular anatomy of the mouse primary motor cortex

Nature ◽  
2021 ◽  
Vol 598 (7879) ◽  
pp. 159-166
Author(s):  
Rodrigo Muñoz-Castañeda ◽  
Brian Zingg ◽  
Katherine S. Matho ◽  
Xiaoyin Chen ◽  
Quanxin Wang ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Brain Function ◽  
Single Neuron ◽  
Primary Motor Cortex ◽  
Projection Neuron ◽  
Mammalian Brain ◽  
Neuron Reconstruction ◽  
Multi Scale ◽  
Structural Framework ◽  
Cellular Resolution

AbstractAn essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input–output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture.

scholarly journals A novel approach for locating mice brain regions of Cryptococcus neoformans CNS invasion

2016 ◽  
Vol 11 ◽  
pp. S136-S143
Author(s):  
Chunting He ◽  
Qingfen Chen ◽  
Longkun Zhu
Keyword(s):  
Motor Cortex ◽  
Cryptococcus Neoformans ◽  
Primary Motor Cortex ◽  
Thalamic Nucleus ◽  
Molecular Layer ◽  
Brain Regions ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Novel Approach ◽  
Stratum Lucidum ◽  
Lateral Posterior

Aim of this study was to locate the brain regions where Cryptococcus interact with brain cells and invade into brain. After 7 days of intratracheal inocula-tion of GFP-tagged Cryptococcus neoformans strains H99, serial cryosections (10 ?m) from 3 C57 BL/6 J mice brains were imaged with immunofluorescence microscopy. GFP-tagged H99 were found in some brain regions such as primary motor cortex-secondary motor cortex, caudate putamen, stratum lucidum of hippocampus, field CA1 of hippocampus, dorsal lateral geniculate nucleus, lateral posterior thalamic nucleus, laterorostral part, lateral posterior thalamic nucleus, mediorostral part, retrosplenial agranular cortex, lateral area of secondary visual cortex, and lacunosum molecular layer of the hippocampus. The results will be very useful for further exploring the mechanism of C. neoformans infection of brain. 

scholarly journals Comparative cellular analysis of motor cortex in human, marmoset and mouse

Nature ◽  
2021 ◽  
Vol 598 (7879) ◽  
pp. 111-119 ◽  
Author(s):  
Trygve E. Bakken ◽  
Nikolas L. Jorstad ◽  
Qiwen Hu ◽  
Blue B. Lake ◽  
Wei Tian ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Neuronal Cell ◽  
Cell Types ◽  
Morphological Characterization ◽  
Fine Motor ◽  
Marker Genes ◽  
Cell Type ◽  
Regulatory Pathways ◽  
Cellular Analysis

AbstractThe primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

scholarly journals Imaging Subthreshold Voltage Oscillation With Cellular Resolution in the Inferior Olive in vitro

2020 ◽  
Vol 14 ◽  
Author(s):  
Kevin Dorgans ◽  
Bernd Kuhn ◽  
Marylka Yoe Uusisaari
Keyword(s):  
Inferior Olive ◽  
Brain Slices ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Wide Field ◽  
Voltage Imaging ◽  
Subthreshold Oscillations ◽  
Cellular Resolution

Voltage imaging with cellular resolution in mammalian brain slices is still a challenging task. Here, we describe and validate a method for delivery of the voltage-sensitive dye ANNINE-6plus (A6+) into tissue for voltage imaging that results in higher signal-to-noise ratio (SNR) than conventional bath application methods. The not fully dissolved dye was injected into the inferior olive (IO) 0, 1, or 7 days prior to acute slice preparation using stereotactic surgery. We find that the voltage imaging improves after an extended incubation period in vivo in terms of labeled volume, homogeneous neuropil labeling with saliently labeled somata, and SNR. Preparing acute slices 7 days after the dye injection, the SNR is high enough to allow single-trial recording of IO subthreshold oscillations using wide-field (network-level) as well as high-magnification (single-cell level) voltage imaging with a CMOS camera. This method is easily adaptable to other brain regions where genetically-encoded voltage sensors are prohibitively difficult to use and where an ultrafast, pure electrochromic sensor, like A6+, is required. Due to the long-lasting staining demonstrated here, the method can be combined, for example, with deep-brain imaging using implantable GRIN lenses.

scholarly journals A multimodal cell census and atlas of the mammalian primary motor cortex

2020 ◽  
Author(s):  
◽  
Ricky S. Adkins ◽  
Andrew I. Aldridge ◽  
Shona Allen ◽  
Seth A. Ament ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Single Cell ◽  
Primary Motor Cortex ◽  
Spatial Information ◽  
Molecular Genetic ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Open Chromatin ◽  
Cell Type ◽  
Spatially Resolved

ABSTRACTWe report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

Abstract 25: Periinfarct Rewiring Supports Recovery After Primary Motor Cortex Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Mitsouko van Assche ◽  
Elisabeth Dirren ◽  
Alexia Bourgeois ◽  
Andreas Kleinschmidt ◽  
Jonas Richiardi ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Spatial Scales ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Relative Increase ◽  
Motor Recovery ◽  
The Core ◽  
Hand Dexterity ◽  
Motor Network

Background and Purpose: After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with motor recovery involves the periinfarct or more remote brain regions. In humans, the challenge is to recruit patients with similar lesions in size and location. Methods: We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were studied at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of motor recovery were investigated at three spatial scales, i) ipsilesional non-infarcted M1, ii) core motor network (including M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Results: Hand dexterity was impaired only in the acute phase ( P =0.036). At a small spatial scale, improved dexterity was associated with increased FC involving mainly the ipsilesional non-infarcted M1 and contralesional motor regions (cM1: rho=0.732; P =0.004; cPMC: rho=0.837, P <0.001; cSMA: rho=0.736; P =0.004). At a larger scale, motor recovery correlated with the relative increase in total FC strength in the core motor network compared to the extended motor network (rho=0.71; P =0.006). Conclusions: FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. The ipsilesional non-infarcted M1 and core motor regions could hence be primary targets for future restorative therapies.

scholarly journals All Talk and No Action: A Transcranial Magnetic Stimulation Study of Motor Cortex Activation during Action Word Production

2004 ◽  
Vol 16 (3) ◽  
pp. 374-381 ◽  
Author(s):  
Massimiliano Oliveri ◽  
Chiara Finocchiaro ◽  
Kevin Shapiro ◽  
Massimo Gangitano ◽  
Alfonso Caramazza ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Brain Regions ◽  
Word Production ◽  
Grammatical Category ◽  
Paired Pulse ◽  
Motor Areas

A number of researchers have proposed that the premotor and motor areas are critical for the representation of words that refer to actions, but not objects. Recent evidence against this hypothesis indicates that the left premotor cortex is more sensitive to grammatical differences than to conceptual differences between words. However, it may still be the case that other anterior motor regions are engaged in processing a word's sensorimotor features. In the present study, we used singleand paired-pulse transcranial magnetic stimulation to test the hypothesis that left primary motor cortex is activated during the retrieval of words (nouns and verbs) associated with specific actions. We found that activation in the motor cortex increased for action words compared with non-action words, but was not sensitive to the grammatical category of the word being produced. These results complement previous findings and support the notion that producing a word activates some brain regions relevant to the sensorimotor properties associated with that word regardless of its grammatical category.

scholarly journals Repetitive transcranial magnetic stimulation restores altered functional connectivity of central poststroke pain model monkeys

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshinori Kadono ◽  
Keigo Koguchi ◽  
Ken-ichi Okada ◽  
Koichi Hosomi ◽  
Motoki Hiraishi ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Functional Connectivity ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Structural Connectivity ◽  
Brain Regions ◽  
Functional Changes ◽  
Therapeutic Mechanism

AbstractCentral poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP.

scholarly journals Aging-Related Changes in Cortical Sources of Sleep Oscillatory Neural Activity Following Motor Learning Reflect Contributions of Cortical Thickness and Pre-sleep Functional Activity

2022 ◽  
Vol 13 ◽  
Author(s):  
Ahren B. Fitzroy ◽  
Bethany J. Jones ◽  
Kyle A. Kainec ◽  
Jeehye Seo ◽  
Rebecca M. C. Spencer
Keyword(s):  
Older Adults ◽  
Motor Cortex ◽  
Motor Learning ◽  
Cortical Thickness ◽  
Neural Activity ◽  
Primary Motor Cortex ◽  
Supplementary Motor Area ◽  
Brain Regions ◽  
Theta Activity ◽  
Oscillatory Activity

Oscillatory neural activity during sleep, such as that in the delta and sigma bands, is important for motor learning consolidation. This activity is reduced with typical aging, and this reduction may contribute to aging-related declines in motor learning consolidation. Evidence suggests that brain regions involved in motor learning contribute to oscillatory neural activity during subsequent sleep. However, aging-related differences in regional contributions to sleep oscillatory activity following motor learning are unclear. To characterize these differences, we estimated the cortical sources of consolidation-related oscillatory activity using individual anatomical information in young and older adults during non-rapid eye movement sleep after motor learning and analyzed them in light of cortical thickness and pre-sleep functional brain activation. High-density electroencephalogram was recorded from young and older adults during a midday nap, following completion of a functional magnetic resonance imaged serial reaction time task as part of a larger experimental protocol. Sleep delta activity was reduced with age in a left-weighted motor cortical network, including premotor cortex, primary motor cortex, supplementary motor area, and pre-supplementary motor area, as well as non-motor regions in parietal, temporal, occipital, and cingulate cortices. Sleep theta activity was reduced with age in a similar left-weighted motor network, and in non-motor prefrontal and middle cingulate regions. Sleep sigma activity was reduced with age in left primary motor cortex, in a non-motor right-weighted prefrontal-temporal network, and in cingulate regions. Cortical thinning mediated aging-related sigma reductions in lateral orbitofrontal cortex and frontal pole, and partially mediated delta reductions in parahippocampal, fusiform, and lingual gyri. Putamen, caudate, and inferior parietal cortex activation prior to sleep predicted frontal and motor cortical contributions to sleep delta and theta activity in an age-moderated fashion, reflecting negative relationships in young adults and positive or absent relationships in older adults. Overall, these results support the local sleep hypothesis that brain regions active during learning contribute to consolidation-related neural activity during subsequent sleep and demonstrate that sleep oscillatory activity in these regions is reduced with aging.

scholarly journals Multiscale Co-Expression in the Brain

2020 ◽  
Author(s):  
Benjamin D. Harris ◽  
Megan Crow ◽  
Stephan Fischer ◽  
Jesse Gillis
Keyword(s):  
Motor Cortex ◽  
Single Cell ◽  
Rna Sequencing ◽  
Primary Motor Cortex ◽  
Cell Types ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific ◽  
The Brain ◽  
Regulatory Landscape

ABSTRACTSingle-cell RNA-sequencing (scRNAseq) data can reveal co-regulatory relationships between genes that may be hidden in bulk RNAseq due to cell type confounding. Using the primary motor cortex data from the Brain Initiative Cell Census Network (BICCN), we study cell type specific co-expression across 500,000 cells. Surprisingly, we find that the same gene-gene relationships that differentiate cell types are evident at finer and broader scales, suggesting a consistent multiscale regulatory landscape.

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