What is a cell type and how to define it?

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

Published: July 1, 2022

Language: Английский

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A transcriptomic axis predicts state modulation of cortical interneurons

Nature, Journal Year: 2022, Volume and Issue: 607(7918), P. 330 - 338

Published: July 6, 2022

Abstract Transcriptomics has revealed that cortical inhibitory neurons exhibit a great diversity of fine molecular subtypes 1–6 , but it is not known whether these have correspondingly diverse patterns activity in the living brain. Here we show primary visual cortex (V1) correlates with brain state, which are organized by single factor: position along main axis transcriptomic variation. We combined vivo two-photon calcium imaging mouse V1 method to identify mRNA for 72 selected genes ex slices. classified imaged layers 1–3 into three-level hierarchy 5 subclasses, 11 types and 35 using previously defined clusters 3 . Responses stimuli differed significantly only between cells Sncg subclass uniformly suppressed, other subclasses predominantly excited. Modulation state at all hierarchical levels could be largely predicted from first principal component, also correlations simultaneously recorded cells. Inhibitory fired more resting, oscillatory states had smaller fraction their axonal projections layer 1, narrower spikes, lower input resistance weaker adaptation as determined vitro 7 expressed cholinergic receptors. Subtypes during arousal opposite properties. Thus, simple principle may explain how shape state-dependent processing.

Language: Английский

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Two-photon calcium imaging of neuronal activity

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: Sept. 1, 2022

Language: Английский

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Cortical somatostatin interneuron subtypes form cell-type-specific circuits

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

Published: June 29, 2023

Language: Английский

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Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex

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

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Long-term intravital subcellular imaging with confocal scanning light-field microscopy

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 27, 2024

Abstract Long-term observation of subcellular dynamics in living organisms is limited by background fluorescence originating from tissue scattering or dense labeling. Existing confocal approaches face an inevitable tradeoff among parallelization, resolution and phototoxicity. Here we present scanning light-field microscopy (csLFM), which integrates axially elongated line-confocal illumination with the rolling shutter (sLFM). csLFM enables high-fidelity, high-speed, three-dimensional (3D) imaging at near-diffraction-limit both optical sectioning low By simultaneous 3D excitation detection, intensity can be reduced below 1 mW mm − 2 , 15-fold higher signal-to-background ratio over sLFM. We imaged 25,000 timeframes optically challenging environments different species, such as migrasome delivery mouse spleen, retractosome generation liver voltage Drosophila . Moreover, facilitates large-scale neural recording crosstalk, leading to high orientation selectivity visual stimuli, similar two-photon microscopy, aids understanding coding mechanisms.

Language: Английский

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Inhibitory specificity from a connectomic census of mouse visual cortex

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

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Dense functional and molecular readout of a circuit hub in sensory cortex

Science, Journal Year: 2022, Volume and Issue: 375(6576)

Published: Jan. 6, 2022

Although single-cell transcriptomics of the neocortex has uncovered more than 300 putative cell types, whether this molecular classification predicts distinct functional roles is unclear. We combined two-photon calcium imaging with spatial to functionally and molecularly investigate cortical circuits. characterized behavior-related responses across major neuronal subclasses in layers 2 or 3 primary somatosensory cortex as mice performed a tactile working memory task. identified an excitatory intratelencephalic type, Baz1a, that exhibits high feature selectivity. Baz1a neurons homeostatically maintain stimulus responsiveness during altered experience show persistent enrichment subsets immediately early genes. Functional anatomical connectivity reveals residing upper portions preferentially innervate somatostatin-expressing inhibitory neurons. This motif defines circuit hub orchestrates local sensory processing superficial neocortex.

Language: Английский

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Molecularly targetable cell types in mouse visual cortex have distinguishable prediction error responses

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2918 - 2928.e8

Published: Sept. 1, 2023

Predictive processing postulates the existence of prediction error neurons in cortex. Neurons with both negative and positive response properties have been identified layer 2/3 visual cortex, but whether they correspond to transcriptionally defined subpopulations is unclear. Here we used activity-dependent, photoconvertible marker CaMPARI2 tag mouse cortex during stimuli behaviors designed evoke errors. We performed single-cell RNA-sequencing on these populations found that previously annotated Adamts2 Rrad transcriptional cell types were enriched when photolabeling drive or responses, respectively. Finally, validated results functionally by designing artificial promoters for use AAV vectors express genetically encoded calcium indicators. Thus, distinct can be targeted using exhibit distinguishable responses.

Language: Английский

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Spatial Transcriptomics: Technical Aspects of Recent Developments and Their Applications in Neuroscience and Cancer Research

Advanced Science, Journal Year: 2023, Volume and Issue: 10(16)

Published: April 7, 2023

Spatial transcriptomics is a newly emerging field that enables high-throughput investigation of the spatial localization transcripts and related analyses in various applications for biological systems. By transitioning from conventional studies to "in situ" biology, can provide transcriptome-scale information. Currently, ability simultaneously characterize gene expression profiles cells relevant cellular environment paradigm shift studies. In this review, recent progress its neuroscience cancer are highlighted. Technical aspects existing technologies future directions new developments (as March 2023), computational analysis transcriptome data, application notes studies, discussions regarding multi-omics their expanding roles biomedical emphasized.

Language: Английский

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