Biology subjects

Serratosa Capdevila, L.

Publications and source records attributed to Serratosa Capdevila, L..

8 recordsLinked to original sources

bioRxiv2026

Cell type-resolved connectomic reconstruction of the spinal dorsal horn reveals sensory neuron synaptic organization and modality-specific inhibition

Touch, temperature, chemical, and noxious stimuli are detected by more than a dozen peripheral sensory neuron subtypes that together mediate somatosensation. Somatosensory neurons form synapses in the spinal cord dorsal horn, the first site of central somatosensory processing, to engage the downstream circuitry that drives both spinal reflexes and ascending pathways for perception. Yet how sensory neuron synapses are organized into the spinal cord circuitry remains poorly understood. Here we present two connectomic tools for studying somatosensory circuits of the spinal cord dorsal horn: dSC1, a large-scale, synapse-resolved electron microscopy (EM) dataset of the mouse dorsal horn, and SPINE (SPinal cord Integrated NEuron classifier), a deep-learning pipeline that identifies major sensory neuron subtypes directly from EM images. Applying SPINE to the dSC1 dataset, we found marked heterogeneity in synaptic architecture across physiologically distinct sensory neuron subtypes: low-threshold mechanoreceptors form substantially more synapses and receive far more GABAergic presynaptic inhibition than high-threshold mechanoreceptors, thermoreceptors and nociceptors. Cell-type-resolved circuit reconstruction further identified five populations of spinal inhibitory neurons (IhNs) that form synapses onto sensory neuron axons, each preferentially driven by and presynaptically inhibiting a single sensory subtype - a homotypic, modality-specific inhibitory motif. Most of these IhNs also feedforwardly inhibit other sensory pathways - a heterotypic, cross modality motif. Together, dSC1 and SPINE enable cell-type-resolved spinal cord circuit reconstruction and reveal a dual-mode logic of sensory-evoked inhibition that shapes modality-specific signaling at the earliest stage of somatosensory processing.

neuroscience↗

bioRxiv2026

A synaptic wiring diagram underlying modality-specific ascending pathways of the superficial spinal dorsal horn

The spinal cord dorsal horn transforms tactile, thermal, pruritic, and nociceptive signals from peripheral somatosensory neurons into outputs to the brain, but how dorsal horn circuits organize diverse inputs into modality-selective ascending pathways is poorly understood. Using dSC1, a large-scale electron microscopy dataset of the mouse dorsal horn, we mapped the circuitry connecting primary sensory afferents to projection neurons of the anterolateral tract (ALT), a principal pathway conveying somatosensory information to the brain. We find that afferents encoding distinct modalities are routed onto connectivity-defined populations of ALT projection neurons. Nociceptors and cold thermoreceptors directly innervate distinct lamina I ALT projection neuron populations specialized for conveying noxious and cooling signals, respectively, whereas tactile and pruritic signals instead pass through a recurrent, multilayered network involving interneurons called vertical cells before reaching a separate ALT projection population. This distinction, direct versus polysynaptic wiring, underlies marked differences in sensory convergence and establishes segregated ascending channels for conveying signals encoding the principal somatosensory modalities. Together, our findings define an architectural logic by which the dorsal horn integrates and routes tactile, thermal, pruritic, and nociceptive information into distinct ALT output pathways to the brain.

neuroscience↗

bioRxiv2026

Structured Connectivity Across Multiple Drosophila Mushroom Bodies

Learning and memory depend on plasticity within neural circuits, but the extent to which the underlying architecture of memory networks is stereotyped or structured remains unclear. Random connectivity may maximise stimulus discrimination, whereas structured connectivity could preferentially route behaviourally relevant information. Here, we compare five adult Drosophila melanogaster Mushroom Body (MB) hemispheres across three connectomes and establish a unified cross-connectome framework for uniglomerular projection neurons (uPNs), Kenyon Cells (KCs), Mushroom Body Output Neurons (MBONs) and Lateral Horn Centrifugal Neurons (LHCENTs). Despite variation in KC abundance and fine-scale connectivity, we identify reproducible organisation across the uPN[->]KC and KC[->]MBON pathways. Food-associated uPN channels consistently contact a greater proportion of KCs than expected by chance, and this bias is preferentially routed through KCs towards approach-promoting MBONs. Sensory input also remains stereotyped across sister MBONs from the same hemisphere despite variation in their individual KC partners. Finally, recurrent LHCENT feedback (predicted-inhibitory) preferentially targets KCs receiving these food-associated inputs. Together, these findings show that a memory network can accommodate local variability while preserving structured pathways that prioritise ethologically relevant sensory information.

neuroscience↗

bioRxiv2026

Deep conservation of head direction circuits in bees, ants and flies

To navigate, animal brains must continuously estimate the bodys heading in space and compare it with internal goals to guide movement. In the fruit fly Drosophila melanogaster a neural circuit in the central complex of the brain serves as an internal compass, exploiting a network architecture called a ring attractor1, 2. While this region is highly conserved and involved in navigation in many insects3, 4, it remains unclear whether the fly circuit represents a general blueprint for head direction computation, or whether different ecologies have driven distinct circuit solutions. Using synaptic-resolution circuit mapping, we identified homologous head direction networks in bees and ants and compared them to the fly circuit. We show that the insect head direction network is conserved across at least 300 million years of evolution. At the level of cell types and projection patterns, all studied species share a nearly identical neural layout, both qualitatively and quantitatively. At the synaptic level, however, the fly and bee circuits differed fundamentally. The distinct wiring principles of homologous neurons expose highly evolvable elements within this otherwise stable circuit. Using these differences in circuit architecture to constrain computational models, we show that both the bee and fly circuits can effectively function as ring attractors with similar, yet distinct, properties. These results demonstrate that complex neural circuits can remain stable over many hundreds of millions of years, while still offering access points for evolution to flexibly adjust neural computations to changing ecological demands, illustrating how evolution balances stability and flexibility in brain circuits.

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bioRxiv2025

A Developmental Atlas of the Drosophila Nerve Cord Uncovers a Global Temporal Code for Neuronal Identity

The assembly of functional neural circuits relies on the generation of diverse neural types with precise molecular identity and connectivity. Unlocking general principles of neuronal specification and wiring across the nervous system requires a systematic and high-resolution characterisation of its diversity, recently enabled by advances in single-cell transcriptomics and connectomics. However, linking the molecular identity of neurons to circuit architecture remains a key challenge. Here, we present a high-resolution developmental transcriptional atlas for the Drosophila melanogaster nerve cord, the central hub for sensory-motor circuits. With an unprecedented 38x aggregate coverage relative to its reference connectome1,2, our atlas captures extensive molecular diversity and enables robust alignment to the adult connectome. We identified three developmental principles underlying neuronal diversity in the nerve cord. First, timing of neurogenesis shapes diversification of molecular identity: embryonic-born neurons diverge faster than larval-born neurons, as also observed in the adult connectome. Second, 17 transcription factors common to neurons from all lineages provide a global molecular identity code for birth order. Lastly, by mapping sex-specific transcriptional profiles to the connectome, we uncovered female-specific apoptosis and transcriptional divergence as key global drivers of sex-specification. By revealing key organisational axes of molecular identity, this atlas opens new avenues to dissect the molecular mechanisms underpinning the development and evolution of neural circuits.

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bioRxiv2024

Comparative connectomics of the descending and ascending neurons of the Drosophila nervous system: stereotypy and sexual dimorphism

In most complex nervous systems there is a clear anatomical separation between the nerve cord, which contains most of the final motor outputs necessary for behaviour, and the brain. In insects, the neck connective is both a physical and information bottleneck connecting the brain and the ventral nerve cord (VNC, spinal cord analogue) and comprises diverse populations of descending (DN), ascending (AN) and sensory ascending neurons, which are crucial for sensorimotor signalling and control. Integrating three separate EM datasets, we now provide a complete connectomic description of the ascending and descending neurons of the female nervous system of Drosophila and compare them with neurons of the male nerve cord. Proofread neuronal reconstructions have been matched across hemispheres, datasets and sexes. Crucially, we have also matched 51% of DN cell types to light level data defining specific driver lines as well as classifying all ascending populations. We use these results to reveal the general architecture, tracts, neuropil innervation and connectivity of neck connective neurons. We observe connected chains of descending and ascending neurons spanning the neck, which may subserve motor sequences. We provide a complete description of sexually dimorphic DN and AN populations, with detailed analysis of circuits implicated in sex-related behaviours, including female ovipositor extrusion (DNp13), male courtship (DNa12/aSP22) and song production (AN hemilineage 08B). Our work represents the first EM-level circuit analyses spanning the entire central nervous system of an adult animal.

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bioRxiv2023

Fine-grained descending control of steering in walking Drosophila

Locomotion involves rhythmic limb movement patterns that originate in circuits outside the brain. Purposeful locomotion requires descending commands from the brain, but we do not understand how these commands are structured. Here we investigate this issue, focusing on the control of steering in walking Drosophila. First, we describe different limb "gestures" associated with different steering maneuvers. Next, we identify a set of descending neurons whose activity predicts steering. Focusing on two descending cell types downstream from distinct brain networks, we show that they evoke specific limb gestures: one lengthens strides on the outside of a turn, while the other attenuates strides on the inside of a turn. Notably, a single descending neuron can have opposite effects during different locomotor rhythm phases, and we identify networks positioned to implement this phase-specific gating. Together, our results show how purposeful locomotion emerges from brain cells that drive specific, coordinated modulations of low-level patterns.

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bioRxiv2021

Striatum-projecting prefrontal cortex neurons support working memory maintenance

The medial prefrontal cortex (mPFC) and the dorsomedial striatum (dmStr) are linked to working memory (WM) but how striatum-projecting mPFC neurons contribute to WM encoding, maintenance, or retrieval remains unclear. Here, we probed mPFC[->]dmStr pathway function in freely-moving mice during a T-maze alternation test of spatial WM. Fiber photometry of GCaMP6m-labeled mPFC[->]dmStr projection neurons revealed strongest activity during the delay period that requires WM maintenance. Demonstrating causality, optogenetic inhibition of mPFC[->]dmStr neurons only during the delay period impaired performance. Conversely, enhancing mPFC[->]dmStr pathway activity--via pharmacological suppression of HCN1 or by optogenetic activation during the delay-- alleviated WM impairment induced by NMDA receptor blockade. Consistently, cellular-resolution miniscope imaging resolved preferred activation of >50% mPFC[->]dmStr neurons during WM maintenance. This subpopulation was distinct from neurons showing preference for encoding and retrieval. In all periods, including the delay, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.

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