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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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Functional connectomics spanning multiple areas of mouse visual cortex

Nature, Год журнала: 2025, Номер 640(8058), С. 435 - 447

Опубликована: Апрель 9, 2025

Abstract Understanding the brain requires understanding neurons’ functional responses to circuit architecture shaping them. Here we introduce MICrONS connectomics dataset with dense calcium imaging of around 75,000 neurons in primary visual cortex (VISp) and higher areas (VISrl, VISal VISlm) an awake mouse that is viewing natural synthetic stimuli. These data are co-registered electron microscopy reconstruction containing more than 200,000 cells 0.5 billion synapses. Proofreading a subset yielded reconstructions include complete dendritic trees as well local inter-areal axonal projections map up thousands cell-to-cell connections per neuron. Released open-access resource, this includes tools for retrieval analysis 1,2 . Accompanying studies describe its use comprehensive characterization cell types 3–6 , synaptic level connectivity diagram cortical column 4 uncovering cell-type-specific inhibitory can be linked gene expression 4,7 Functionally, identify new computational principles how information integrated across space 8 characterize novel neuronal invariances 9 bring structure function together uncover general principle between excitatory within 10,11

Язык: Английский

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Inhibitory specificity from a connectomic census of mouse visual cortex

Nature, Год журнала: 2025, Номер 640(8058), С. 448 - 458

Опубликована: Апрель 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.

Язык: Английский

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Petascale pipeline for precise alignment of images from serial section electron microscopy

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 4, 2024

Abstract The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy often limited the preceding step aligning 2D to create a 3D stack. Precise and robust alignment in presence artifacts challenging, especially as datasets are attaining petascale. We present computational pipeline for ssEM with several key elements. Self-supervised convolutional nets trained via metric learning encode align pairs, they used initialize iterative fine-tuning alignment. A procedure called vector voting increases robustness or missing data. For speedup series divided into blocks that distributed workers aligned each other composing transformations decay, which achieves global without resorting time-consuming optimization. apply our whole fly brain dataset, show improved relative prior state art. also demonstrate scales cubic millimeter mouse visual cortex. Our publicly available through two open source Python packages.

Язык: Английский

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Large-scale neurophysiology and single-cell profiling in human neuroscience

Nature, Год журнала: 2024, Номер 630(8017), С. 587 - 595

Опубликована: Июнь 19, 2024

Язык: Английский

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Functional connectomics spanning multiple areas of mouse visual cortex

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Июль 29, 2021

Abstract To understand the brain we must relate neurons’ functional responses to circuit architecture that shapes them. Here, present a large connectomics dataset with dense calcium imaging of millimeter scale volume. We recorded activity from approximately 75,000 neurons in primary visual cortex (VISp) and three higher areas (VISrl, VISal VISlm) an awake mouse viewing natural movies synthetic stimuli. The data were co-registered volumetric electron microscopy (EM) reconstruction containing more than 200,000 cells 0.5 billion synapses. Subsequent proofreading subset this volume yielded reconstructions include complete dendritic trees as well local inter-areal axonal projections map up thousands cell-to-cell connections per neuron. release open-access resource scientific community including set tools facilitate retrieval downstream analysis. In accompanying papers describe our findings using provide comprehensive structural characterization cortical cell types 1–3 most detailed synaptic level connectivity diagram column date 2 , uncovering unique cell-type specific inhibitory motifs can be linked gene expression 4 . Functionally, identify new computational principles how information is integrated across space 5 characterize novel neuronal invariances 6 bring structure function together decipher general principle wires excitatory within 7, 8

Язык: Английский

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Fast imaging of millimeter-scale areas with beam deflection transmission electron microscopy

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 10, 2024

Serial section transmission electron microscopy (TEM) has proven to be one of the leading methods for millimeter-scale 3D imaging brain tissues at nanoscale resolution. It is important further improve efficiency acquire larger and more volumes. We report here a threefold increase in speed TEM by using beam deflecting mechanism enable highly efficient acquisition multiple image tiles (nine) each motion mechanical stage. For areas, duty cycle doubles than 30%, yielding net average rate 0.3 gigapixels per second. If fully utilized, an array four deflection TEMs should capable dataset cubic millimeter scale five weeks.

Язык: Английский

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Intensity Inhomogeneity Correction for Large Panoramic Electron Microscopy Images

Lecture notes in computer science, Год журнала: 2025, Номер unknown, С. 45 - 54

Опубликована: Янв. 1, 2025

Язык: Английский

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Size-dependent penetration depth of colloidal nanoparticles into cell spheroids

Advanced Drug Delivery Reviews, Год журнала: 2025, Номер 222, С. 115593 - 115593

Опубликована: Май 6, 2025

Язык: Английский

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Plasmodium falciparumdisruption of pericyte angiopoietin-1 secretion contributes to barrier breakdown in a 3D brain microvessel model

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 29, 2024

Abstract Disruption of the vascular protective angiopoietin-Tie axis is common in cerebral malaria (CM) patients, with elevated angiopoietin-2 (Ang-2) and reduced angiopoietin-1 (Ang-1) blood concentrations. The role pericytes CM pathogenesis remains unexplored, despite being a major source brain Ang-1 secretion evidence pericyte damage observed postmortem samples. Here we engineered 3D microfluidics-based microvessel model containing both human primary microvascular endothelial cells pericytes. This replicated vessel coverage ultrastructural interactions present microvasculature. When exposed to P. falciparum -iRBC egress products, microvessels presented decreased secretion, increased permeability, minor changes morphology. Notably, -mediated barrier disruption was partially reversed after pre-treatment recombinant Ang-1. Our approach suggests novel mechanistic highlights importance dysfunction caused by .

Язык: Английский

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