Neuronal wiring diagram of an adult brain

Nature, Год журнала: 2024, Номер 634(8032), С. 124 - 138

Опубликована: Окт. 2, 2024

Язык: Английский

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Neurite Exchange Imaging (NEXI): A minimal model of diffusion in gray matter with inter-compartment water exchange

NeuroImage, Год журнала: 2022, Номер 256, С. 119277 - 119277

Опубликована: Май 3, 2022

Biophysical models of diffusion in white matter are based on what is now commonly referred to as the "Standard Model" (SM) non-exchanging anisotropic Gaussian compartments. In this work, we focus MRI gray matter, which requires rethinking basic microstructure modeling blocks. particular, at least three contributions beyond SM need be considered: water exchange across cell membrane - between neurites and extracellular space; non-Gaussian along neuronal glial processes resulting from structural disorder; signal contribution soma. For first contribution, propose Neurite Exchange Imaging (NEXI) an extension diffusion, builds K\"arger model two exchanging Using datasets acquired multiple weightings (b) times (t) rat brain vivo, show that for investigated time window (~10-45 ms) there minimal diffusivity time-dependence more pronounced kurtosis decay with well fit by model. Moreover, observe lower longer high b. light these observations, identify mechanism best explains signatures both low-b high-b regime, thereby NEXI mapping. We finally highlight multi-b multi-t acquisitions protocols being suited estimate parameters reliably. approach, inter-compartment 15 60 ms cortex hippocampus same order or shorter than typical acquisitions. This suggests essential component interpreting measurements matter.

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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Perisomatic ultrastructure efficiently classifies cells in mouse cortex

Nature, Год журнала: 2025, Номер 640(8058), С. 478 - 486

Опубликована: Апрель 9, 2025

Abstract Mammalian neocortex contains a highly diverse set of cell types. These types have been mapped systematically using variety molecular, electrophysiological and morphological approaches 1–4 . Each modality offers new perspectives on the variation biological processes underlying cell-type specialization. Cellular-scale electron microscopy provides dense ultrastructural examination an unbiased perspective subcellular organization brain cells, including their synaptic connectivity nanometre-scale morphology. In data that contain tens thousands neurons, most which incomplete reconstructions, identifying becomes clear challenge for analysis 5 Here, to address this challenge, we present systematic survey somatic region all cells in cubic millimetre cortex quantitative features obtained from microscopy. This demonstrates perisomatic is sufficient identify types, defined primarily basis patterns. We then describe how classification facilitates cell-type-specific characterization locating with rare patterns dataset.

Язык: Английский

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NEURD offers automated proofreading and feature extraction for connectomics

Nature, Год журнала: 2025, Номер 640(8058), С. 487 - 496

Опубликована: Апрель 9, 2025

We are in the era of millimetre-scale electron microscopy volumes collected at nanometre resolution1,2. Dense reconstruction cellular compartments these has been enabled by recent advances machine learning3-6. Automated segmentation methods produce exceptionally accurate reconstructions cells, but post hoc proofreading is still required to generate large connectomes that free merge and split errors. The elaborate 3D meshes neurons contain detailed morphological information multiple scales, from diameter, shape branching patterns axons dendrites, down fine-scale structure dendritic spines. However, extracting features can require substantial effort piece together existing tools into custom workflows. Here, building on open source software for mesh manipulation, we present Neural Decomposition (NEURD), a package decomposes meshed compact extensively annotated graph representations. With feature-rich graphs, automate variety tasks such as state-of-the-art automated errors, cell classification, spine detection, axonal-dendritic proximities other annotations. These enable many downstream analyses neural morphology connectivity, making massive complex datasets more accessible neuroscience researchers.

Язык: Английский

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Light-microscopy-based connectomic reconstruction of mammalian brain tissue

Nature, Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Abstract The information-processing capability of the brain’s cellular network depends on physical wiring pattern between neurons and their molecular functional characteristics. Mapping resolving individual synaptic connections can be achieved by volumetric imaging at nanoscale resolution 1,2 with dense labelling. Light microscopy is uniquely positioned to visualize specific molecules, but dense, synapse-level circuit reconstruction light has been out reach, owing limitations in resolution, contrast capability. Here we describe light-microscopy-based connectomics (LICONN). We integrated specifically engineered hydrogel embedding expansion comprehensive deep-learning-based segmentation analysis connectivity, thereby directly incorporating information into reconstructions brain tissue. LICONN will allow phenotyping tissue biological experiments a readily adoptable manner.

Язык: Английский

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Connectomics of the Octopus vulgaris vertical lobe provides insight into conserved and novel principles of a memory acquisition network

eLife, Год журнала: 2023, Номер 12

Опубликована: Июль 6, 2023

Here, we present the first analysis of connectome a small volume

Язык: Английский

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Diffusion-based deep learning method for augmenting ultrastructural imaging and volume electron microscopy

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

Опубликована: Июнь 1, 2024

Abstract Electron microscopy (EM) revolutionized the way to visualize cellular ultrastructure. Volume EM (vEM) has further broadened its three-dimensional nanoscale imaging capacity. However, intrinsic trade-offs between speed and quality of restrict attainable area volume. Isotropic with vEM for large biological volumes remains unachievable. Here, we developed EMDiffuse, a suite algorithms designed enhance capabilities, leveraging cutting-edge image generation diffusion model. EMDiffuse generates realistic predictions high resolution ultrastructural details exhibits robust transferability by taking only one pair images 3 megapixels fine-tune in denoising super-resolution tasks. also demonstrated proficiency isotropic reconstruction task, generating volume even absence training data. We robustness from seven public datasets obtained different techniques instruments. The generated enables accurate ultrastructure analysis. features self-assessment functionalities on predictions’ reliability. envision pave investigations intricate subcellular within systems.

Язык: Английский

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THE R. GLENN NORTHCUTT COLLECTION OF COMPARATIVE VERTEBRATE NEUROANATOMY AND EMBRYOLOGY: A NOVEL MUSEUM-BASED RESOURCE FOR NEUROSCIENCE AND EVOLUTIONARY BIOLOGY

Bulletin of the Museum of Comparative Zoology, Год журнала: 2025, Номер 163(10)

Опубликована: Янв. 17, 2025

In 2019, the Harvard Museum of Comparative Zoology acquired The R. Glenn Northcutt Collection Vertebrate Neuroanatomy and Embryology, which comprises an estimated 500,000 histologic sections whole mounts prepared mounted on glass slides. Assembled by Professor between 1963 2014 to reveal microscopic anatomy nervous system related tissues, collection additionally includes valuable slide series other neuroanatomists, including John Black Johnston, Othmar Solnitzky, David Senn. Most included specimens are serially sectioned or partial brains for comparative cytoarchitectonic studies. There also entire heads hundreds embryos representing 22 genera studies development sensory systems cranial nerves. is scientifically unique in its taxonomic breadth: more than 240 270 species represent all major groups living vertebrates as well two key out-groups, acorn worms cephalochordates. Particular strengths include hagfishes, lampreys, chondrichthyans, basal actinopterygians, sarcopterygians (including lungfishes coelacanth, Latimeria), amphibians, tuatara (Sphenodon), many families squamates, turtles, crocodilians, marsupials, primates. Ongoing curatorial activities generating digital whole-slide images most collection, accessible via Internet. Here we briefly describe history scientific importance, methods used prepare slides, ancillary materials, doctoral postdoctoral students visiting scientists who utilized it their studies, a list publications based slides and, finally, inventory information that will facilitate use research education.

Язык: Английский

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