Cell type-resolved connectomic reconstruction of the spinal dorsal horn reveals sensory neuron synaptic organization and modality-specific inhibition
- 1Harvard Medical School, FM Kirby Neurobiology Center, Boston Children's Hospital
Abstract
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.
Related
- ESCRT-I Inhibition Protects against NMDAR Hypofunction and Restores Synaptic Homeostasis in a Cellular Model of Schizophrenia
- LATS2 modulates synaptic organization and function by regulating actin dynamics
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization
- Ion modulation restores local synaptic function in APOE4 neuronal networks despite persistent impairments in global network organization
- Temporal Organization of Synaptic Input and Intrinsic Excitability Shape Direction Selectivity in the Developing Xenopus laevis Optic Tectum
BibTeX
@misc{xiang2026cell,
title = {{Cell type-resolved connectomic reconstruction of the spinal dorsal horn reveals sensory neuron synaptic organization and modality-specific inhibition}},
author = {W. Xiang and K. Delgado and Q. Zhang and J. Turecek and A. Holtrup and R. Khajeh and T. Nguyen and J. A. Bae and A. Halageri and N. Kemnitz and T. Macrina and D. Zhang and S. Cameron and B. Moya-Llamas and M. F. Mazri and J. Ni and R. Roberts and A. Schildkamp and L. Serratosa Capdevila and A. Norton and J. Liu and M. Liu and S. Dorkenwald and D. L. Paul and D. D. Ginty and W.-C. A. Lee},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.27.754691},
url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754691v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cell type-resolved connectomic reconstruction of the spinal dorsal horn reveals sensory neuron synaptic organization and modality-specific inhibition
AU - W. Xiang
AU - K. Delgado
AU - Q. Zhang
AU - J. Turecek
AU - A. Holtrup
AU - R. Khajeh
AU - T. Nguyen
AU - J. A. Bae
AU - A. Halageri
AU - N. Kemnitz
AU - T. Macrina
AU - D. Zhang
AU - S. Cameron
AU - B. Moya-Llamas
AU - M. F. Mazri
AU - J. Ni
AU - R. Roberts
AU - A. Schildkamp
AU - L. Serratosa Capdevila
AU - A. Norton
AU - J. Liu
AU - M. Liu
AU - S. Dorkenwald
AU - D. L. Paul
AU - D. D. Ginty
AU - W.-C. A. Lee
PY - 2026
DA - 2026/09/27
PB - bioRxiv
DO - 10.64898/2026.09.27.754691
UR - https://www.biorxiv.org/content/10.64898/2026.09.27.754691v1
AB - 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.
ER -