What is a cell type and how to define it?

Cell, Год журнала: 2022, Номер 185(15), С. 2739 - 2755

Опубликована: Июль 1, 2022

Язык: Английский

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The connectome of an insect brain

Science, Год журнала: 2023, Номер 379(6636)

Опубликована: Март 10, 2023

Brains contain networks of interconnected neurons and so knowing the network architecture is essential for understanding brain function. We therefore mapped synaptic-resolution connectome an entire insect ( Drosophila larva) with rich behavior, including learning, value computation, action selection, comprising 3016 548,000 synapses. characterized neuron types, hubs, feedforward feedback pathways, as well cross-hemisphere brain-nerve cord interactions. found pervasive multisensory interhemispheric integration, highly recurrent architecture, abundant from descending neurons, multiple novel circuit motifs. The brain’s most circuits comprised input output learning center. Some structural features, multilayer shortcuts nested loops, resembled state-of-the-art deep architectures. identified provides a basis future experimental theoretical studies neural circuits.

Язык: Английский

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Reconstruction of neocortex: Organelles, compartments, cells, circuits, and activity

Cell, Год журнала: 2022, Номер 185(6), С. 1082 - 1100.e24

Опубликована: Фев. 24, 2022

Язык: Английский

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A transcriptomic axis predicts state modulation of cortical interneurons

Nature, Год журнала: 2022, Номер 607(7918), С. 330 - 338

Опубликована: Июль 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.

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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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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Hippocampal GABAergic interneurons and memory

Neuron, Год журнала: 2023, Номер 111(20), С. 3154 - 3175

Опубликована: Июль 18, 2023

One of the most captivating questions in neuroscience revolves around brain's ability to efficiently and durably capture store information. It must process continuous input from sensory organs while also encoding memories that can persist throughout a lifetime. What are cellular-, subcellular-, network-level mechanisms underlie this remarkable capacity for long-term information storage? Furthermore, what contributions do distinct types GABAergic interneurons make process? As hippocampus plays pivotal role memory, our review focuses on three aspects: (1) delineation hippocampal interneuron their connectivity, (2) plasticity, (3) activity patterns during memory-related rhythms, including long-range disinhibition. We explore how these elements, together showcasing diversity inhibitory circuits, shape processing hippocampus.

Язык: Английский

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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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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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