Guided Proofreading of Automatic Segmentations for Connectomics

Automatic cell image segmentation methods in connectomics produce merge and split errors, which require correction through proofreading. Previous research has identified the visual search for these errors as the bottleneck in interactive proofreading. To aid error correction, we develop two classifiers that automatically recommend candidate merges and splits to the user. These classifiers use a convolutional neural network (CNN) that has been trained with errors in automatic segmentations against expert-labeled ground truth. Our classifiers detect potentially-erroneous regions by considering a large context region around a segmentation boundary. Corrections can then be performed by a user with yes/no decisions, which reduces variation of information 7.5x faster than previous proofreading methods. We also present a fully-automatic mode that uses a probability threshold to make merge/split decisions. Extensive experiments using the automatic approach and comparing performance of novice and expert users demonstrate that our method performs favorably against state-of-the-art proofreading methods on different connectomics datasets.Comment: Supplemental material available at http://rhoana.org/guidedproofreading/supplemental.pd

Quantitative neuroanatomy for connectomics in Drosophila

Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.Publisher PDFPeer reviewe

A Process for Digitizing and Simulating Biologically Realistic Oligocellular Networks Demonstrated for the Neuro-Glio-Vascular Ensemble

One will not understand the brain without an integrated exploration of structure and function, these attributes being two sides of the same coin: together they form the currency of biological computation. Accordingly, biologically realistic models require the re-creation of the architecture of the cellular components in which biochemical reactions are contained. We describe here a process of reconstructing a functional oligocellular assembly that is responsible for energy supply management in the brain and creating a computational model of the associated biochemical and biophysical processes. The reactions that underwrite thought are both constrained by and take advantage of brain morphologies pertaining to neurons, astrocytes and the blood vessels that deliver oxygen, glucose and other nutrients. Each component of this neuro-glio-vasculature ensemble (NGV) carries-out delegated tasks, as the dynamics of this system provide for each cell-type its own energy requirements while including mechanisms that allow cooperative energy transfers. Our process for recreating the ultrastructure of cellular components and modeling the reactions that describe energy flow uses an amalgam of state-of the-art techniques, including digital reconstructions of electron micrographs, advanced data analysis tools, computational simulations and in silico visualization software. While we demonstrate this process with the NGV, it is equally well adapted to any cellular system for integrating multimodal cellular data in a coherent framework

Quantitative neuroanatomy for connectomics in Drosophila.

Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.Funding came from the HHMI Janelia Visiting Scientist program (AC), Swiss National Science Foundation grant 31003A 132969 (AC), HHMI, and the Institute of Neuroinformatics of the University of Zurich and ETH Zurich.This is the final version of the article. It first appeared from eLife via http://dx.doi.org/10.7554/eLife.12059.00

A connectome and analysis of the adult Drosophila central brain.

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