A connectome and analysis of the adult Drosophila central brain

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Sept. 3, 2020

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction brain fruit fly Drosophila melanogaster . Improved include procedures to prepare, image, align, segment, find synapses in, proofread such data sets. define cell types, refine computational compartments, provide an exhaustive atlas examples many them novel. detailed consisting neurons their chemical most central brain. make public simplify access, reducing effort needed answer circuit questions, linking defined by our analysis with genetic reagents. Biologically, we examine distributions connection strengths, motifs on different scales, electrical consequences compartmentalization, evidence that maximizing packing density is important criterion in evolution fly’s

Language: Английский

---

A connectomic study of a petascale fragment of human cerebral cortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: May 30, 2021

Abstract We acquired a rapidly preserved human surgical sample from the temporal lobe of cerebral cortex. stained 1 mm 3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ∼30 nm and imaged these sections using high-speed multibeam scanning electron microscope. used computational methods to render three-dimensional structure containing 57,216 cells, hundreds millions neurites 133.7 million synaptic connections. The 1.4 petabyte microscopy volume, segmented cell parts, blood vessels, myelin, inhibitory excitatory synapses, 104 manually proofread cells are available peruse online . Many interesting unusual features were evident this dataset. Glia outnumbered neurons 2:1 oligodendrocytes most common type volume. Excitatory spiny comprised 69% neuronal population, synapses also majority (76%). drive onto was biased strongly toward excitation (70%) case for interneurons (48%). Despite incompleteness automated segmentation caused by split merge errors, we could automatically generate (and then validate) connections between neuron types both within layers. In studying found that deep layer can be classified into new subsets, based on structural connectivity differences, chandelier not only innervate initial segments as previously described, but each other’s segments. Furthermore, among thousands weak established neuron, there exist rarer highly powerful axonal inputs establish multi-synaptic contacts (up ∼20 synapses) target neurons. Our analysis indicates strong specific, allow small numbers axons have an outsized role activity some their postsynaptic partners.

Language: Английский

---

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

Cell, Journal Year: 2022, Volume and Issue: 185(6), P. 1082 - 1100.e24

Published: Feb. 24, 2022

Language: Английский

---

Volume electron microscopy

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

Published: July 7, 2022

Language: Английский

---

Oligodendrocyte precursor cells ingest axons in the mouse neocortex

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(48)

Published: Nov. 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.

Language: Английский

---

Binary and analog variation of synapses between cortical pyramidal neurons

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Nov. 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.

Language: Английский

---

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

---

Instance segmentation of mitochondria in electron microscopy images with a generalist deep learning model trained on a diverse dataset

Cell Systems, Journal Year: 2023, Volume and Issue: 14(1), P. 58 - 71.e5

Published: Jan. 1, 2023

Language: Английский

---

Functional connectomics spanning multiple areas of mouse visual cortex

Nature, Journal Year: 2025, Volume and Issue: 640(8058), P. 435 - 447

Published: April 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

Language: Английский

---

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

---