Correlative light and electron microscopy reveals the fine circuit structure underlying evidence accumulation in larval zebrafish

AbstractEvidence accumulation is a fundamental neural computation essential for adaptive behavior, yet its synaptic implementation remains unclear. Addressing this challenge critically depends on linking neural dynamics to circuit structure within the same brain. Here, we combine functional calcium imaging with large-scale ultrastructural electron microscopy (EM) to uncover the wiring logic of visual evidence accumulation in larval zebrafish. In a functionally imaged EM dataset of the anterior hindbrain, we identify conserved morphological cell types whose activity patterns define distinct computational roles. Bilateral inhibition, disinhibition, and recurrent connectivity emerge as key circuit motifs shaping these dynamics. To generalize our findings across animals, we develop a photoconversion-based pipeline to label and reconstruct functionally characterized neurons, enabling us to train a classifier that predicts functional identity from morphology alone. Applying this classifier to a second, whole-brain EM dataset lacking functional data reveals matching connectivity patterns, significantly augmenting its applicability for detailed circuit dissections. Based on these results, we develop and constrain a biophysically realistic neural network model that captures observed dynamics and yields predictions we tested and confirmed experimentally. Our work illustrates how hypothesis-driven connectomics can uncover the synaptic basis of sensory-motor computations and establishes a novel framework for cross-animal circuit dissection in the vertebrate brain.