scholarly journals Topological Sholl Descriptors for Neuronal Clustering and Classification

2021 ◽  
Author(s):  
Reem Khalil ◽  
Sadok Kallel ◽  
Ahmad Farhat ◽  
Paweł Dłotko
Keyword(s):  
Metric Spaces ◽  
Metric Learning ◽  
Functional Characterization ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Neuronal Morphology ◽  
Clustering Methods ◽  
Clustering And Classification

Variations in neuronal morphology among cell classes, brain regions, and animal species are thought to underlie known heterogeneities in neuronal function. Thus, accurate quantitative descriptions and classification of large sets of neurons is essential for functional characterization. However, unbiased computational methods to classify groups of neurons are currently scarce. We introduce a novel, robust, and unbiased method to study neuronal morphologies. We develop mathematical descriptors that quantitatively characterize structural differences among neuronal cell types and thus classify them. Each descriptor that is assigned to a neuron is a function of a distance from the soma with values in real numbers or more general metric spaces. Standard clustering methods enhanced with detection and metric learning algorithms are then used to objectively cluster and classify neurons. Our results illustrate a practical and effective approach to the classification of diverse neuronal cell types, with the potential for discovery of putative subclasses of neurons.

scholarly journals A Deep Learning Approach for the Classification of Neuronal Cell Types

2018 ◽  
Author(s):  
Alessio P. Buccino ◽  
Torbjorn V. Ness ◽  
Gaute T. Einevoll ◽  
Gert Cauwenberghs ◽  
Philipp D. Hafliger
Keyword(s):  
Deep Learning ◽  
Neuronal Cell ◽  
Cell Types ◽  
Learning Approach

scholarly journals Dissecting Cellular Heterogeneity Based on Network Denoising of scRNA-seq Using Local Scaling Self-Diffusion

2022 ◽  
Vol 12 ◽  
Author(s):  
Xin Duan ◽  
Wei Wang ◽  
Minghui Tang ◽  
Feng Gao ◽  
Xudong Lin
Keyword(s):  
Metric Learning ◽  
Cell Types ◽  
Primary Objective ◽  
The Self ◽  
Cellular Heterogeneity ◽  
Clustering Methods ◽  
Local Scaling ◽  
Self Diffusion ◽  
Cell Clustering ◽  
High Level

Identifying the phenotypes and interactions of various cells is the primary objective in cellular heterogeneity dissection. A key step of this methodology is to perform unsupervised clustering, which, however, often suffers challenges of the high level of noise, as well as redundant information. To overcome the limitations, we proposed self-diffusion on local scaling affinity (LSSD) to enhance cell similarities’ metric learning for dissecting cellular heterogeneity. Local scaling infers the self-tuning of cell-to-cell distances that are used to construct cell affinity. Our approach implements the self-diffusion process by propagating the affinity matrices to further improve the cell similarities for the downstream clustering analysis. To demonstrate the effectiveness and usefulness, we applied LSSD on two simulated and four real scRNA-seq datasets. Comparing with other single-cell clustering methods, our approach demonstrates much better clustering performance, and cell types identified on colorectal tumors reveal strongly biological interpretability.

scholarly journals Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

2016 ◽  
Vol 113 (21) ◽  
pp. 6029-6034 ◽  
Author(s):  
Jiang He ◽  
Ruobo Zhou ◽  
Zhuhao Wu ◽  
Monica A. Carrasco ◽  
Peri T. Kurshan ◽  
...  
Keyword(s):  
Glial Cell ◽  
Animal Species ◽  
Homo Sapiens ◽  
Neuronal Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Periodic Distribution ◽  
Neuronal Types

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.

scholarly journals Reconstruction of 1,000 projection neurons reveals new cell types and organization of long-range connectivity in the mouse brain

2019 ◽  
Author(s):  
Johan Winnubst ◽  
Erhan Bas ◽  
Tiago A. Ferreira ◽  
Zhuhao Wu ◽  
Michael N. Economo ◽  
...  
Keyword(s):  
Long Range ◽  
Mouse Brain ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Morphology ◽  
Projection Neurons ◽  
Axonal Arbor ◽  
Flow Of Information ◽  
Organizational Principles ◽  
The Brain

SummaryNeuronal cell types are the nodes of neural circuits that determine the flow of information within the brain. Neuronal morphology, especially the shape of the axonal arbor, provides an essential descriptor of cell type and reveals how individual neurons route their output across the brain. Despite the importance of morphology, few projection neurons in the mouse brain have been reconstructed in their entirety. Here we present a robust and efficient platform for imaging and reconstructing complete neuronal morphologies, including axonal arbors that span substantial portions of the brain. We used this platform to reconstruct more than 1,000 projection neurons in the motor cortex, thalamus, subiculum, and hypothalamus. Together, the reconstructed neurons comprise more than 75 meters of axonal length and are available in a searchable online database. Axonal shapes revealed previously unknown subtypes of projection neurons and suggest organizational principles of long-range connectivity.

scholarly journals FMRP has a cell-type-specific role in CA1 pyramidal neurons to regulate autism-related transcripts and circadian memory

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kirsty Sawicka ◽  
Caryn R Hale ◽  
Christopher Y Park ◽  
John J Fak ◽  
Jodi E Gresack ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Rna Binding ◽  
Fragile X ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Cell Type ◽  
Ca1 Pyramidal Neurons ◽  
Mrna Targets ◽  
Specific Regulation

Loss of the RNA binding protein FMRP causes Fragile X Syndrome (FXS), the most common cause of inherited intellectual disability, yet it is unknown how FMRP function varies across brain regions and cell types and how this contributes to disease pathophysiology. Here we use conditional tagging of FMRP and CLIP (FMRP cTag CLIP) to examine FMRP mRNA targets in hippocampal CA1 pyramidal neurons, a critical cell type for learning and memory relevant to FXS phenotypes. Integrating these data with analysis of ribosome-bound transcripts in these neurons revealed CA1-enriched binding of autism-relevant mRNAs, and CA1-specific regulation of transcripts encoding circadian proteins. This contrasted with different targets in cerebellar granule neurons, and was consistent with circadian defects in hippocampus-dependent memory in Fmr1 knockout mice. These findings demonstrate differential FMRP-dependent regulation of mRNAs across neuronal cell types that may contribute to phenotypes such as memory defects and sleep disturbance associated with FXS.

scholarly journals Single-nuclei transcriptomics of schizophrenia prefrontal cortex primarily implicates neuronal subtypes

2020 ◽  
Author(s):  
Benjamin C. Reiner ◽  
Richard C. Crist ◽  
Lauren M. Stein ◽  
Andrew E. Weller ◽  
Glenn A. Doyle ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Differentially Expressed Genes ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Differentially Expressed ◽  
Inhibitory Neurons ◽  
Specific Cell ◽  
Dorsolateral Prefrontal ◽  
Layer V

AbstractTranscriptomic studies of bulk neural tissue homogenates from persons with schizophrenia and controls have identified differentially expressed genes in multiple brain regions. However, the heterogeneous nature prevents identification of relevant cell types. This study analyzed single-nuclei transcriptomics of ∼311,000 nuclei from frozen human postmortem dorsolateral prefrontal cortex samples from individuals with schizophrenia (n = 14) and controls (n = 16). 2,846 differential expression events were identified in 2,195 unique genes in 19 of 24 transcriptomically-distinct cell populations. ∼97% of differentially expressed genes occurred in five neuronal cell types, with ∼63% occurring in a subtype of PVALB+ inhibitory neurons and HTR2C+ layer V excitatory neurons. Differentially expressed genes were enriched for genes localized to schizophrenia GWAS loci. Cluster-specific changes in canonical pathways, upstream regulators and causal networks were identified. These results expand our knowledge of disrupted gene expression in specific cell types and permit new insight into the pathophysiology of schizophrenia.

scholarly journals Extracellular Interactions of Alpha-Synuclein in Multiple System Atrophy

2018 ◽  
Vol 19 (12) ◽  
pp. 4129 ◽  
Author(s):  
Dario Valdinocci ◽  
Rowan Radford ◽  
Michael Goulding ◽  
Junna Hayashi ◽  
Roger Chung ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Disease Process ◽  
Neuronal Cell ◽  
Cell Loss ◽  
Cell Types ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Current Evidence ◽  
Extracellular Milieu ◽  
The Brain

Multiple system atrophy, characterized by atypical Parkinsonism, results from central nervous system (CNS) cell loss and dysfunction linked to aggregates of the normally pre-synaptic α-synuclein protein. Mostly cytoplasmic pathological α-synuclein inclusion bodies occur predominantly in oligodendrocytes in affected brain regions and there is evidence that α-synuclein released by neurons is taken up preferentially by oligodendrocytes. However, extracellular α-synuclein has also been shown to interact with other neural cell types, including astrocytes and microglia, as well as extracellular factors, mediating neuroinflammation, cell-to-cell spread and other aspects of pathogenesis. Here, we review the current evidence for how α-synuclein present in the extracellular milieu may act at the cell surface to drive components of disease progression. A more detailed understanding of the important extracellular interactions of α-synuclein with neuronal and non-neuronal cell types both in the brain and periphery may provide new therapeutic targets to modulate the disease process.

scholarly journals Extracellular spike waveform dissociates four functionally distinct cell classes in primate cortex

2019 ◽  
Author(s):  
Caterina Trainito ◽  
Constantin von Nicolai ◽  
Earl K. Miller ◽  
Markus Siegel
Keyword(s):  
Visual Information ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Frontal Eye Field ◽  
Visual Response ◽  
Cell Type ◽  
Response Dynamics ◽  
Distinct Cell ◽  
Behaving Monkeys

SummaryUnderstanding the function of different neuronal cell types is key to understanding brain function. However, cell type diversity is typically overlooked in electrophysiological studies in awake behaving animals. Here, we show that four functionally distinct cell classes can be robustly identified from extracellular recordings in several cortical regions of awake behaving monkeys. We recorded extracellular spiking activity from dorsolateral prefrontal cortex (dlPFC), the frontal eye field (FEF), and the lateral intraparietal area of macaque monkeys during a visuomotor decision-making task. We employed unsupervised clustering of spike waveforms, which robustly dissociated four distinct cell classes across all three brain regions. The four cell classes were functionally distinct. They showed different baseline firing statistics, visual response dynamics, and coding of visual information. While cell class-specific baseline statistics were consistent across brain regions, response dynamics and information coding were regionally specific. Our results identify four waveform-based cell classes in primate cortex. This opens a new window to dissect and study the cell-type specific function of cortical circuits.

scholarly journals Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains

2019 ◽  
Author(s):  
Ekaterina Khrameeva ◽  
Ilia Kurochkin ◽  
Dingding Han ◽  
Patricia Guijarro ◽  
Sabina Kanton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Human Cognition ◽  
Human Lineage ◽  
Cell Type ◽  
Cell Nuclei ◽  
Tissue Samples ◽  
Cell Type Specific

ABSTRACTIdentification of gene expression traits unique to the human brain sheds light on the mechanisms of human cognition. Here we searched for gene expression traits separating humans from other primates by analyzing 88,047 cell nuclei and 422 tissue samples representing 33 brain regions of humans, chimpanzees, bonobos, and macaques. We show that gene expression evolves rapidly within cell types, with more than two-thirds of cell type-specific differences not detected using conventional RNA sequencing of tissue samples. Neurons tend to evolve faster in all hominids, but non-neuronal cell types, such as astrocytes and oligodendrocyte progenitors, show more differences on the human lineage, including alterations of spatial distribution across neocortical layers.

scholarly journals Permeabilization-free en bloc immunohistochemistry for correlative microscopy

2020 ◽  
Author(s):  
Kara A Fulton ◽  
Kevin L Briggman
Keyword(s):  
Electron Microscopy ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Synaptic Proteins ◽  
En Bloc ◽  
Two Photon ◽  
Tissue Sections ◽  
3D Electron Microscopy ◽  
3D Electron

AbstractA dense reconstruction of neuronal synaptic connectivity typically requires high-resolution 3D electron microscopy (EM) data, but EM data alone lacks functional information about neurons and synapses. One approach to augment structural EM datasets is with the fluorescent immunohistochemical (IHC) localization of functionally relevant proteins. We describe a protocol that obviates the requirement of tissue permeabilization in thick tissue sections, a major impediment for correlative pre-embedding IHC and EM. We demonstrate the permeabilization-free labeling of neuronal cell types, intracellular enzymes, and synaptic proteins in tissue sections hundreds of microns thick in multiple brain regions while simultaneously retaining the ultrastructural integrity of the tissue. Finally, we explore the utility of this protocol by performing proof-of-principle correlative experiments combining two-photon imaging of protein distributions and 3D electron microscopy.

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