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Holtrup, A.

Publications and source records attributed to Holtrup, A..

2 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↗