Multimodal cortical neuronal cell type classification DOI Creative Commons

Xiaoyi Mao,

Jochen F. Staiger

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: 476(5), P. 721 - 733

Published: Feb. 20, 2024

Abstract Since more than a century, neuroscientists have distinguished excitatory (glutamatergic) neurons with long-distance projections from inhibitory (GABAergic) local and established layer-dependent schemes for the ~ 80% (principal) cells as well 20% neurons. Whereas, in early days, mainly morphological criteria were used to define cell types, later supplemented by electrophysiological neurochemical properties, nowadays. single-cell transcriptomics is method of choice type classification. Bringing recent insight together, we conclude that despite all layer- area-dependent differences, there set reliably identifiable cortical types named (among others) intratelencephalic (IT), extratelencephalic (ET), corticothalamic (CT) cells, which altogether comprise 56 transcriptomic (t-types). By same means, subdivided into parvalbumin (PV), somatostatin (SST), vasoactive intestinal polypeptide (VIP), “other (i.e. Lamp5/Sncg)” subpopulations, 60 t-types. The coming years will show t-types actually translate “real” common multimodal features, including not only transcriptome but also physiology morphology connectivity ultimately function. Only better knowledge clear-cut experimental access them, be able reveal their specific functions, task turned out difficult part brain being so much specialized cognition cerebral cortex.

Language: Английский

What is a cell type and how to define it? DOI Creative Commons
Hongkui Zeng

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

Citations

294
Molecularly defined and spatially resolved cell atlas of the whole mouse brain DOI Creative Commons
Meng Zhang, Xingjie Pan, Won Jung

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 343 - 354

Published: Dec. 13, 2023

In mammalian brains, millions to billions of cells form complex interaction networks enable a wide range functions. The enormous diversity and intricate organization have impeded our understanding the molecular cellular basis brain function. Recent advances in spatially resolved single-cell transcriptomics enabled systematic mapping spatial molecularly defined cell types tissues1-3, including several regions (for example, refs. 1-11). However, comprehensive atlas whole is still missing. Here we imaged panel more than 1,100 genes approximately 10 million across entire adult mouse brains using multiplexed error-robust fluorescence situ hybridization12 performed resolved, expression profiling at whole-transcriptome scale by integrating hybridization RNA sequencing data. Using this approach, generated 5,000 transcriptionally distinct clusters, belonging 300 major types, with high resolution. Registration common coordinate framework allowed quantifications cell-type composition individual regions. We further identified modules characterized compositions gradients featuring gradual changes cells. Finally, high-resolution map cells, each transcriptome-wide profile, us infer cell-type-specific interactions between hundreds pairs predict (ligand-receptor) functional implications these cell-cell interactions. These results provide rich insights into architecture foundation for investigations neural circuits their dysfunction health disease.

Language: Английский

Citations

230
Insights into Alzheimer’s disease from single-cell genomic approaches DOI
Mitchell H. Murdock, Li‐Huei Tsai

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(2), P. 181 - 195

Published: Jan. 2, 2023

Language: Английский

Citations

104
Spatial omics technologies at multimodal and single cell/subcellular level DOI Creative Commons
Jiwoon Park, Junbum Kim,

Tyler Lewy

et al.

Genome biology, Journal Year: 2022, Volume and Issue: 23(1)

Published: Dec. 13, 2022

Abstract Spatial omics technologies enable a deeper understanding of cellular organizations and interactions within tissue interest. These assays can identify specific compartments or regions in with differential transcript protein abundance, delineate their interactions, complement other methods defining phenotypes. A variety spatial methodologies are being developed commercialized; however, these techniques differ resolution, multiplexing capability, scale/throughput, coverage. Here, we review the current prospective landscape single cell to subcellular resolution analysis tools provide comprehensive picture for both research clinical applications.

Language: Английский

Citations

78
Cortical somatostatin interneuron subtypes form cell-type-specific circuits DOI
Jingjing Sherry Wu, Elaine Sevier, Deepanjali Dwivedi

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(17), P. 2675 - 2692.e9

Published: June 29, 2023

Language: Английский

Citations

76
Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex DOI Creative Commons
Casey M Schneider-Mizell, Ágnes L. Bodor, Derrick Brittain

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 24, 2023

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here, we used millimeter-scale volumetric electron microscopy 1 to investigate all inhibitory neurons across densely-segmented population 1352 cells spanning layers mouse visual cortex, producing wiring diagram connections more than 70,000 synapses. Taking data-driven approach inspired by classical neuroanatomy, classified based on relative targeting dendritic compartments other developed novel classification excitatory morphological synaptic input The between revealed class disinhibitory specialist basket cells, addition familiar subclasses. Analysis onto found widespread specificity, many interneurons exhibiting differential certain subpopulations spatially intermingled potential targets. Inhibitory was organized into “motif groups,” diverse sets that collectively target both perisomatic same Collectively, our analysis identified new organizing principles for inhibition will serve as foundation linking modern multimodal atlases diagram.

Language: Английский

Citations

60
Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex DOI
Thomas Chartrand, Rachel Dalley, Jennie Close

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6667)

Published: Oct. 12, 2023

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion human neocortex marked by distinctive pyramidal neurons with extensive L1 branching, but whether interneurons are similarly diverse underexplored. Using Patch-seq recordings from neurosurgical tissue, we identified four transcriptomic subclasses mouse homologs, along distinct subtypes types unmatched in L1. Subclass subtype comparisons showed stronger differences were correlated strong morphoelectric variability dimensions variability. Accompanied greater thickness other cytoarchitecture changes, these findings suggest that has diverged evolution, reflecting the demands regulating expanded neocortical circuit.

Language: Английский

Citations

58
Inhibitory specificity from a connectomic census of mouse visual cortex DOI Creative Commons
Casey M Schneider-Mizell, Ágnes L. Bodor, Derrick Brittain

et al.

Nature, Journal Year: 2025, Volume and Issue: 640(8058), P. 448 - 458

Published: April 9, 2025

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate all inhibitory neurons across densely segmented population 1,352 cells spanning layers mouse visual cortex, producing wiring diagram inhibition more than 70,000 synapses. Inspired by classical neuroanatomy, classified based on targeting dendritic compartments developed an excitatory neuron classification reconstructions whole-cell maps synaptic input. Single-cell showed class disinhibitory specialist that targets basket cells. Analysis onto found widespread specificity, many interneurons exhibiting differential spatially intermingled subpopulations. Inhibitory was organized into 'motif groups', diverse sets collectively target both perisomatic same targets. Collectively, our analysis identified new organizing principles for will serve as foundation linking contemporary multimodal atlases diagram.

Language: Английский

Citations

8
Transcriptomic neuron types vary topographically in function and morphology DOI Creative Commons
Inbal Shainer, Johannes M. Kappel,

Eva Laurell

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract Neuronal phenotypic traits such as morphology, connectivity and function are dictated, to a large extent, by specific combination of differentially expressed genes. Clusters neurons in transcriptomic space correspond distinct cell types some cases—for example, Caenorhabditis elegans 1 retinal ganglion cells 2–4 —have been shown share morphology function. The zebrafish optic tectum is composed spatial array that transforms visual inputs into motor outputs. Although the visuotopic map continuous, subregions functionally specialized 5,6 . Here, uncover cell-type architecture tectum, we transcriptionally profiled its neurons, revealing more than 60 organized anatomical layers. We measured responses thousands tectal two-photon calcium imaging matched them with their transcriptional profiles. Furthermore, characterized morphologies identified using transgenic lines. Notably, found similar can diverge shape, responses. Incorporating coordinates within volume revealed morphologically defined subclusters individual clusters. Our findings demonstrate extrinsic, position-dependent factors expand repertoire genetically neurons.

Language: Английский

Citations

5
Multimodal mapping of cell types and projections in the central nucleus of the amygdala DOI Creative Commons
Yuhan Wang, Sabine Krabbe, Mark Eddison

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 20, 2023

The central nucleus of the amygdala (CEA) is a brain region that integrates external and internal sensory information executes innate adaptive behaviors through distinct output pathways. Despite its complex functions, diversity molecularly defined neuronal types in CEA their contributions to major axonal projection targets have not been examined systematically. Here, we performed single-cell RNA-sequencing (scRNA-seq) classify cell identified marker genes map location these using expansion-assisted iterative fluorescence situ hybridization (EASI-FISH). We developed new methods integrate EASI-FISH with 5-plex retrograde labeling determine spatial, morphological, connectivity properties ~30,000 neurons. Our study revealed spatiomolecular organization CEA, medial lateral associated families. also found long-range axon network from where target regions receive inputs multiple types. Axon collateralization was primarily among projections hindbrain targets, which are forebrain projections. This resource reports gene combinations for axon-projection types, will be useful selective interrogation populations diverse functions CEA.

Language: Английский

Citations

44