ArticleeLife2015
Extracellular space preservation aids the connectomic analysis of neural circuits.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
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- Comparative connectomics reveals stage-specific gap junction rewiring that reshapes avoidance behavior.bioRxiv : the preprint server for biology · 2026Article
- Synaptic-resolution connectomics: towards large brains and connectomic screening.Nature reviews. Neuroscience · 2026Review
- Cryopreservation of aldehyde-fixed whole brains.PloS one · 2026Article
- Nondestructive X-ray tomography of brain tissue ultrastructure.Nature methods · 2025Article
- Emergence of Functional Heart-Brain Circuits in a Vertebrate.bioRxiv : the preprint server for biology · 2025Article
- Correlative light and electron microscopy reveals the fine circuit structure underlying evidence accumulation in larval zebrafish.bioRxiv : the preprint server for biology · 2025Article
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- Mechanical perfusion in brain banking: methods of assessment and relationship to the postmortem interval.Free neuropathology · 2025Article
- Evaluating ultrastructural preservation quality in banked brain tissue.Free neuropathology · 2025Article
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- GAUSS-EM, guided accumulation of ultrathin serial sections with a static magnetic field for volume electron microscopy.Cell reports methods · 2024Article
- Immersion Fixation and Staining of Multicubic Millimeter Volumes for Electron Microscopy-Based Connectomics of Human Brain Biopsies.Biological psychiatry · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Dense connectomic mapping of neuronal circuits is limited by the time and effort required to analyze 3D electron microscopy (EM) datasets. Algorithms designed to automate image segmentation suffer from substantial error rates and require significant manual error correction. Any improvement in segmentation error rates would therefore directly reduce the time required to analyze 3D EM data. We explored preserving extracellular space (ECS) during chemical tissue fixation to improve the ability to segment neurites and to identify synaptic contacts. ECS preserved tissue is easier to segment using machine learning algorithms, leading to significantly reduced error rates. In addition, we observed that electrical synapses are readily identified in ECS preserved tissue. Finally, we determined that antibodies penetrate deep into ECS preserved tissue with only minimal permeabilization, thereby enabling correlated light microscopy (LM) and EM studies. We conclude that preservation of ECS benefits multiple aspects of the connectomic analysis of neural circuits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.