Cellular-resolution Connectomics: Challenges of Dense Neural Circuit Reconstruction

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2013 Jun 1

PMID 23722209

Citations 112

Authors

Moritz Helmstaedter

Affiliations

Soon will be listed here.

Abstract

Neuronal networks are high-dimensional graphs that are packed into three-dimensional nervous tissue at extremely high density. Comprehensively mapping these networks is therefore a major challenge. Although recent developments in volume electron microscopy imaging have made data acquisition feasible for circuits comprising a few hundreds to a few thousands of neurons, data analysis is massively lagging behind. The aim of this perspective is to summarize and quantify the challenges for data analysis in cellular-resolution connectomics and describe current solutions involving online crowd-sourcing and machine-learning approaches.

Citing Articles

Dense, continuous membrane labeling and expansion microscopy visualization of ultrastructure in tissues.

Shin T, Wang H, Zhang C, An B, Lu Y, Zhang E Nat Commun. 2025; 16(1):1579.

PMID: 39939319 PMC: 11821914. DOI: 10.1038/s41467-025-56641-z.

Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells.

Gonschorek D, Goldin M, Oesterle J, Schwerd-Kleine T, Arlinghaus R, Zhao Z Elife. 2025; 13.

PMID: 39783858 PMC: 11717361. DOI: 10.7554/eLife.98742.

A hierarchically annotated dataset drives tangled filament recognition in digital neuron reconstruction.

Chen W, Liao M, Bao S, An S, Li W, Liu X Patterns (N Y). 2024; 5(8):101007.

PMID: 39233689 PMC: 11368685. DOI: 10.1016/j.patter.2024.101007.

Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity.

Turegano-Lopez M, de Las Pozas F, Santuy A, Rodriguez J, DeFelipe J, Merchan-Perez A Commun Biol. 2024; 7(1):796.

PMID: 38951162 PMC: 11217374. DOI: 10.1038/s42003-024-06491-0.

Automated neuronal reconstruction with super-multicolour Tetbow labelling and threshold-based clustering of colour hues.

Leiwe M, Fujimoto S, Baba T, Moriyasu D, Saha B, Sakaguchi R Nat Commun. 2024; 15(1):5279.

PMID: 38918382 PMC: 11199630. DOI: 10.1038/s41467-024-49455-y.

References

Craddock R, Jbabdi S, Yan C, Vogelstein J, Castellanos F, Di Martino A . Imaging human connectomes at the macroscale. Nat Methods. 2013; 10(6):524-39. PMC: 4096321. DOI: 10.1038/nmeth.2482. View

Helmstaedter M, Briggman K, Turaga S, Jain V, Seung H, Denk W . Connectomic reconstruction of the inner plexiform layer in the mouse retina. Nature. 2013; 500(7461):168-74. DOI: 10.1038/nature12346. View

Fahrenbach W . Anatomical circuitry of lateral inhibition in the eye of the horseshoe crab, Limulus polyphemus. Proc R Soc Lond B Biol Sci. 1985; 225(1239):219-49. DOI: 10.1098/rspb.1985.0060. View

Turaga S, Murray J, Jain V, Roth F, Helmstaedter M, Briggman K . Convolutional networks can learn to generate affinity graphs for image segmentation. Neural Comput. 2009; 22(2):511-38. DOI: 10.1162/neco.2009.10-08-881. View

Kreshuk A, Straehle C, Sommer C, Koethe U, Cantoni M, Knott G . Automated detection and segmentation of synaptic contacts in nearly isotropic serial electron microscopy images. PLoS One. 2011; 6(10):e24899. PMC: 3198725. DOI: 10.1371/journal.pone.0024899. View

Chicurel M, Harris K . Three-dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus. J Comp Neurol. 1992; 325(2):169-82. DOI: 10.1002/cne.903250204. View

Fiala J . Reconstruct: a free editor for serial section microscopy. J Microsc. 2005; 218(Pt 1):52-61. DOI: 10.1111/j.1365-2818.2005.01466.x. View

Chklovskii D, Vitaladevuni S, Scheffer L . Semi-automated reconstruction of neural circuits using electron microscopy. Curr Opin Neurobiol. 2010; 20(5):667-75. DOI: 10.1016/j.conb.2010.08.002. View

Rancz E, Franks K, Schwarz M, Pichler B, Schaefer A, Margrie T . Transfection via whole-cell recording in vivo: bridging single-cell physiology, genetics and connectomics. Nat Neurosci. 2011; 14(4):527-32. PMC: 3501644. DOI: 10.1038/nn.2765. View

10.

Feldmeyer D, Lubke J, Silver R, Sakmann B . Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column. J Physiol. 2002; 538(Pt 3):803-22. PMC: 2290091. DOI: 10.1113/jphysiol.2001.012959. View

11.

Andres B, Koethe U, Kroeger T, Helmstaedter M, Briggman K, Denk W . 3D segmentation of SBFSEM images of neuropil by a graphical model over supervoxel boundaries. Med Image Anal. 2012; 16(4):796-805. DOI: 10.1016/j.media.2011.11.004. View

12.

Cooper S, Khatib F, Treuille A, Barbero J, Lee J, Beenen M . Predicting protein structures with a multiplayer online game. Nature. 2010; 466(7307):756-60. PMC: 2956414. DOI: 10.1038/nature09304. View

13.

Butcher N, Friedrich A, Lu Z, Tanimoto H, Meinertzhagen I . Different classes of input and output neurons reveal new features in microglomeruli of the adult Drosophila mushroom body calyx. J Comp Neurol. 2012; 520(10):2185-201. DOI: 10.1002/cne.23037. View

14.

Becker C, Ali K, Knott G, Fua P . Learning context cues for synapse segmentation in EM volumes. Med Image Comput Comput Assist Interv. 2013; 15(Pt 1):585-92. DOI: 10.1007/978-3-642-33415-3_72. View

15.

Roberts M, Jeong W, Vazquez-Reina A, Unger M, Bischof H, Lichtman J . Neural process reconstruction from sparse user scribbles. Med Image Comput Comput Assist Interv. 2011; 14(Pt 1):621-8. DOI: 10.1007/978-3-642-23623-5_78. View

16.

Bock D, Lee W, Kerlin A, Andermann M, Hood G, Wetzel A . Network anatomy and in vivo physiology of visual cortical neurons. Nature. 2011; 471(7337):177-82. PMC: 3095821. DOI: 10.1038/nature09802. View

17.

Varshney L, Chen B, Paniagua E, Hall D, Chklovskii D . Structural properties of the Caenorhabditis elegans neuronal network. PLoS Comput Biol. 2011; 7(2):e1001066. PMC: 3033362. DOI: 10.1371/journal.pcbi.1001066. View

18.

Helmstaedter M, Mitra P . Computational methods and challenges for large-scale circuit mapping. Curr Opin Neurobiol. 2012; 22(1):162-9. PMC: 3406305. DOI: 10.1016/j.conb.2011.11.010. View

19.

Briggman K, Helmstaedter M, Denk W . Wiring specificity in the direction-selectivity circuit of the retina. Nature. 2011; 471(7337):183-8. DOI: 10.1038/nature09818. View

20.

Mishchenko Y, Hu T, Spacek J, Mendenhall J, Harris K, Chklovskii D . Ultrastructural analysis of hippocampal neuropil from the connectomics perspective. Neuron. 2010; 67(6):1009-20. PMC: 3215280. DOI: 10.1016/j.neuron.2010.08.014. View