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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A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution

Science, Год журнала: 2024, Номер 384(6696)

Опубликована: Май 9, 2024

To fully understand how the human brain works, knowledge of its structure at high resolution is needed. Presented here a computationally intensive reconstruction ultrastructure cubic millimeter temporal cortex that was surgically removed to gain access an underlying epileptic focus. It contains about 57,000 cells, 230 millimeters blood vessels, and 150 million synapses comprises 1.4 petabytes. Our analysis showed glia outnumber neurons 2:1, oligodendrocytes were most common cell, deep layer excitatory could be classified on basis dendritic orientation, among thousands weak connections each neuron, there exist rare powerful axonal inputs up 50 synapses. Further studies using this resource may bring valuable insights into mysteries brain.

Язык: Английский

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A multi-scale brain map derived from whole-brain volumetric reconstructions

Nature, Год журнала: 2021, Номер 591(7848), С. 105 - 110

Опубликована: Фев. 24, 2021

Язык: Английский

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Oligodendrocyte precursor cells ingest axons in the mouse neocortex

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(48)

Опубликована: Ноя. 23, 2022

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by engulfment and degradation axonal branches synapses surrounding glial cells, including microglia astrocytes. However, small size phagocytic organelles complex, highly ramified morphology glia have made it difficult to define contribution these other cell types this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation reconstruct complete 3D morphologies distinct mouse visual cortex, providing unprecedented resolution composition. Unexpectedly, discovered that fine processes oligodendrocyte precursor cells (OPCs), a population abundant, dynamic progenitors, frequently surrounded axons. Numerous phagosomes phagolysosomes (PLs) containing fragments axons vesicular structures were present inside processes, suggesting OPCs engage axon pruning. Single-nucleus RNA sequencing from cortex revealed express key genes at stage, well neuronal transcripts, consistent active engulfment. Although are thought be responsible for majority synaptic pruning refinement, PLs ten times more abundant than markedly less newly generated oligodendrocytes, contribute substantially during cortical development.

Язык: Английский

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Glutamate indicators with improved activation kinetics and localization for imaging synaptic transmission

Nature Methods, Год журнала: 2023, Номер 20(6), С. 925 - 934

Опубликована: Май 4, 2023

Abstract The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing variants exhibit low in vivo signal-to-noise ratios, saturating activation kinetics exclusion from postsynaptic densities. Using a multiassay screen bacteria, soluble protein cultured neurons, we generated improved ratios kinetics. We developed surface display constructs that improve iGluSnFR’s nanoscopic localization to postsynapses. resulting iGluSnFR3 exhibits rapid nonsaturating reports synaptic release decreased saturation increased specificity versus extrasynaptic signals neurons. Simultaneous electrophysiology at individual boutons mouse visual cortex showed transients report single action potentials high In vibrissal sensory layer 4, used characterize distinct patterns touch-evoked feedforward input thalamocortical both recurrent onto L4 cortical neuron dendritic spines.

Язык: Английский

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neuPrint: An open access tool for EM connectomics

Frontiers in Neuroinformatics, Год журнала: 2022, Номер 16

Опубликована: Июль 20, 2022

Due to advances in electron microscopy and deep learning, it is now practical reconstruct a connectome, description of neurons the chemical synapses between them, for significant volumes neural tissue. Smaller past reconstructions were primarily used by domain experts, could be handled downloading data, performance was not serious problem. But new much larger upend these assumptions. These networks contain tens thousands millions connections, with yet pending, are interest large community non-specialists. Allowing other scientists make use this data needs more than publication-it requires tools that publicly available, easy use, efficiently handle data. We introduce neuPrint address analysis challenges. Neuprint contains two major components-a web interface programmer APIs. The designed allow any scientist worldwide, using only browser, quickly ask answer typical biological queries about connectome. APIs computer-savvy complex or higher volume queries. NeuPrint also provides features assessing reconstruction quality. Internally, organizes connectome as graph stored neo4j database. This gives high queries, access though public well documented query language Cypher, will extend future connectomics databases. Our experience an experiment open science. find fraction readers article proceed examine directly. In our case preprints worked exactly intended, inquiries PDF downloads starting immediately after pre-print publication, little affected formal publication later. From we deduce many interested suggesting data-only papers can appreciated release speed up propagation scientific results months. providing, keeping, available online imposes substantial additional costs research.

Язык: Английский

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Neuropathic pain caused by miswiring and abnormal end organ targeting

Nature, Год журнала: 2022, Номер 606(7912), С. 137 - 145

Опубликована: Май 25, 2022

Abstract Nerve injury leads to chronic pain and exaggerated sensitivity gentle touch (allodynia) as well a loss of sensation in the areas which injured non-injured nerves come together 1–3 . The mechanisms that disambiguate these mixed paradoxical symptoms are unknown. Here we longitudinally non-invasively imaged genetically labelled populations fibres sense noxious stimuli (nociceptors) (low-threshold afferents) peripherally skin for longer than 10 months after nerve injury, while simultaneously tracking pain-related behaviour same mice. Fully denervated initially lost sensation, gradually recovered normal developed marked allodynia aversion several injury. This reinnervation-induced neuropathic involved nociceptors sprouted into territories precisely reproducing initial pattern innervation, were guided by blood vessels showed irregular terminal connectivity lowered activation thresholds mimicking low-threshold afferents. By contrast, afferents—which normally mediate intact 4–7 —did not reinnervate, leading an aberrant innervation tactile end organs such Meissner corpuscles with alone. Genetic ablation fully abrogated reinnervation allodynia. Our results thus reveal emergence form is driven structural plasticity, abnormal malfunction during reinnervation, provide mechanistic framework sensory manifestations observed clinically can impose heavy burden on patients.

Язык: Английский

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Diffusion time dependence, power-law scaling, and exchange in gray matter

NeuroImage, Год журнала: 2022, Номер 251, С. 118976 - 118976

Опубликована: Фев. 7, 2022

Diffusion MRI (dMRI) provides contrast that reflect diffusing spins' interactions with microstructural features of biological systems, but its specificity remains limited due to the ambiguity relation underlying microstructure. To improve specificity, biophysical models white matter (WM) typically express dMRI signals according Standard Model (SM) and have more recently in gray (GM) attempted incorporate cell soma (the SANDI model). The validity assumptions these models, however, largely undetermined, especially GM. Observing models' unique, functional properties, such as $b^{-1/2}$ power-law associated 1d diffusion, has emerged a fruitful strategy for experimental validation. absence this signature GM been explained by neurite water exchange, non-linear morphology, and/or obscuring signal contributions. Here, we present simulations realistic neurons demonstrating curvature branching does not destroy stick impermeable neurites, their is drowned under typical conditions: Nevertheless, identify an attainable regime which dominates. Furthermore, find exchange-driven time dependence produces behavior opposite expected from restricted thereby providing disambiguating two effects. We data experiments ex vivo rat brain at ultrahigh field observe consistent substantial exchange power-law. first finding suggests significant while second small sub-population neurites. quantify our observations, harness K\"arger model corresponding SM SANDI.

Язык: Английский

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Vision-dependent specification of cell types and function in the developing cortex

Cell, Год журнала: 2022, Номер 185(2), С. 311 - 327.e24

Опубликована: Янв. 1, 2022

Язык: Английский

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Binary and analog variation of synapses between cortical pyramidal neurons

eLife, Год журнала: 2022, Номер 11

Опубликована: Ноя. 16, 2022

Learning from experience depends at least in part on changes neuronal connections. We present the largest map of connectivity to date between cortical neurons a defined type (layer 2/3 [L2/3] pyramidal cells mouse primary visual cortex), which was enabled by automated analysis serial section electron microscopy images with improved handling image defects (250 × 140 90 μm3 volume). used identify constraints learning algorithms employed cortex. Previous studies modeled continuum synapse sizes log-normal distribution. A is consistent most neural network models learning, synaptic strength continuously graded analog variable. Here, we show that size, when restricted synapses L2/3 cells, well sum binary variable and an drawn Two sharing same presynaptic postsynaptic are known be correlated size. variables two highly correlated, while not. Binary variation could outcome Hebbian or other plasticity rule depending activity signals relatively uniform across arbors, may dominated influences such as spontaneous dynamical fluctuations. discuss implications for longstanding hypothesis activity-dependent switches bistable states.

Язык: Английский

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