Biology subjects

Merfeld, K.

Publications and source records attributed to Merfeld, K..

2 recordsLinked to original sources

bioRxiv2026

Connectome quality converges predictably to reveal optimal stopping points during proofreading

Volumetric electron microscopy (EM) has become a critical approach to generating high-resolution reconstructions of brain tissue. As the size of EM volumes increase, use of automated image segmentation within the reconstruction pipeline has become essential, although it generates errors that need correction. The proofreading and correcting of these errors has since become the dominant cost driver in the pipeline, but precisely estimating the sufficient number of proofreading edits to enable meaningful scientific analyses of the reconstructed neuronal networks remains a challenge. We present a fast, computationally inexpensive way to estimate the progress of a connectomic proofreading effort without requiring a priori knowledge of ground truth. We show that simple global graph invariants converge predictably to asymptotic limits with increasing numbers of proofreading edits, informing a quantitative "pencils down" criterion for proofreading completeness. We illustrate our method on two datasets in different stages of proofreading progress, a zebrafish spinal cord and the hemibrain Drosophila melanogaster dataset. Our method reduces the uncertainty associated with the planning and prioritization of proofreading activities and enables data owners to accurately predict and budget the amount of proofreading necessary for their scientific questions.

neuroscience↗

bioRxiv2026

Physical contact reveals a hidden layer of cortical architecture

Neurons interact at synapses, but they also communicate through physical contact and proximity, including diffusion, glia-mediated interactions, and ephaptic coupling. Standard connectomes map synapses, but cannot capture the full set of cell-cell contacts that can support these pathways. Here we extract contactomes from two large mouse visual cortex volumes at nanoscale resolution and quantify every cell-cell contact, the shared surface area of each contact, and the relationship between contact and synaptic connectivity. We find that contactomes are 5 - 10x denser than synaptic graphs, revealing that neurons physically contact a much larger set of potential neighbors than they synaptically connect to. We further find that most nearby potential neighbors are already in physical contact, indicating that local structural change would add few new candidate synaptic partners. Finally, we find that astrocytes form a single large syncytium-like network that spans the tissue and directly contacts nearly all neurons, and that glial processes lie within a micron or two of almost every synapse, indicating that synapses reside within a pervasive glia-shaped microenvironment. Together, these results show that physical contact forms a distinct layer of brain architecture that extends far beyond the synaptic connectome.

neuroscience↗