A connectomic resource for neural cataloguing and circuit dissection of the larval zebrafish brain

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bioRxiv. 2025 Jun 16;. doi: 10.1101/2025.06.10.658982

A connectomic resource for neural cataloguing and circuit dissection of the larval zebrafish brain Ahrens LabScientific Computing Software Project Pipeline Support

Petkova MD, Januszewski M, Blakely T, Herrera KJ, Schuhknecht GF, Tiller R, Choi J, Schalek RL, Boulanger-Weill J, Peleg A, Wu Y, Wang S, Troidl J, Vohra S, Wei D, Lin Z, Bahl A, Tapia JC, Iyer N, Miller ZT, Hebert KB, Pavarino EC, Taylor M, Deng Z, Stingl M, Hockling D, Hebling A, Wang RC, Zhang LL, Dvorak S, Faik Z, King KI, Goel P, Wagner-Carena J, Aley D, Chalyshkan S, Contreas D, Li X, Muthukumar AV, Vernaglia MS, Carrasco TT, Melnychuck S, Yan T, Dalal A, DiMartino JM, Brown S, Safo-Mensa N, Greenberg E, Cook M, Finley-May S, Flynn MA, Hopkins GP, Kovalyak J, Leonard M, Lohff A, Ordish C, Scott AL, Takemura S, Walsh C, Walsh JJ, Berger DR, Pfister H, Berg S, Knecht C, Meissner GW, Korff W, Ahrens MB, Jain V, Lichtman JW, Engert F

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Abstract

We present a correlated light and electron microscopy (CLEM) dataset from a 7-day-old larval zebrafish, integrating confocal imaging of genetically labeled excitatory (vglut2a) and inhibitory (gad1b) neurons with nanometer-resolution serial section EM. The dataset spans the brain and anterior spinal cord, capturing >180,000 segmented soma, >40,000 molecularly annotated neurons, and 30 million synapses, most of which were classified as excitatory, inhibitory, or modulatory. To characterize the directional flow of activity across the brain, we leverage the synaptic and cell body annotations to compute region-wise input and output drive indices at single cell resolution. We illustrate the dataset’s utility by dissecting and validating circuits in three distinct systems: water flow direction encoding in the lateral line, recurrent excitation and contralateral inhibition in a hindbrain motion integrator, and functionally relevant targeted long-range projections from a tegmental excitatory nucleus, demonstrating that this resource enables rigorous hypothesis testing as well as exploratory-driven circuit analysis. The dataset is integrated into an open-access platform optimized to facilitate community reconstruction and discovery efforts throughout the larval zebrafish brain.

Preprint: https://www.biorxiv.org/content/early/2025/06/15/2025.06.10.658982

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