Rencken, S. | Search bioRxiv

bioRxiv2025

Chromosome-scale genome assembly of the European common cuttlefish Sepia officinalis

Coleoid cephalopods, a subclass of mollusks that includes octopuses, cuttlefish and squid, exhibit sophisticated biological features such as dynamic and neurally driven camouflage behavior, inter-individual communication, single-lens camera-like eyes, the largest brains among invertebrates and a distinctive embryonic development. The common cuttlefish Sepia officinalis has served as a model organism in various research fields, spanning biophysics, neurobiology, behavior, evolution, ecology and biomechanics. More recently, it has become a model to investigate the neural mechanisms underlying cephalopod camouflage, using quantitative behavioral approaches alongside molecular techniques to characterize the identity, evolution and development of neuronal cell types. Despite significant interest in this animal, a high-quality, annotated genome of this species is still lacking. To address this, we sequenced and assembled a chromosome-scale genome for S. officinalis. Our assembly spans 5.68 billion base pairs and comprises 1n=47 repeat-rich chromosome scaffolds. This was unexpected because the haploid karyotypes of other decapods indicate 46 chromosomes. Detailed comparisons of our data to those from published decapod genome assemblies and to another recent genome assembly of S. officinalis (itself suggesting 1n=49 chromosomes) in fact revealed clear homologies between 46 scaffolds across all the datasets. The discrepancies between datasets are explained by highly repetitive regions, impairing proper read alignments. We conclude that the true karyotype of S. officinalis is probably 1n=46 chromosomes, a likely ancestral and if true, conserved decapod karyotype. Our results include a comprehensive gene annotation and full-length transcript prediction, which we used to characterize orthologous gene families across mollusks. We identified several large-scale expansions specific to cephalopods, with many genes specific to neural or non-neural tissues of adult S. officinalis. In summary, this genome should provide a valuable resource for future research on the evolution, brain organization, information processing, development and behavior in this important clade.

genomics↗

bioRxiv2025

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.

neuroscience↗