A synaptic wiring diagram underlying modality-specific ascending pathways of the superficial spinal dorsal horn
- 1Harvard Medical School, HHMI
Abstract
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.
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BibTeX
@misc{xiang2026synaptic,
title = {{A synaptic wiring diagram underlying modality-specific ascending pathways of the superficial spinal dorsal horn}},
author = {W. Xiang and R. Khajeh and K. Delgado and J. Liu and A. Holtrup and Q. Zhang and S. Cameron and T. Nguyen and J. A. Bae and A. Halageri and N. Kemnitz and T. Macrina and B. Moya Llamas and A. Schildkamp and M. F. Mazri and J. Ni and R. Roberts and L. Serratosa Capdevila and R. Wang and A. Dsouza and A. Norton and S. Wang and D. Zhang and P. L. Tang and S. Choi and W.-C. A. Lee and D. D. Ginty},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.27.754843},
url = {https://www.biorxiv.org/content/10.64898/2026.09.27.754843v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A synaptic wiring diagram underlying modality-specific ascending pathways of the superficial spinal dorsal horn
AU - W. Xiang
AU - R. Khajeh
AU - K. Delgado
AU - J. Liu
AU - A. Holtrup
AU - Q. Zhang
AU - S. Cameron
AU - T. Nguyen
AU - J. A. Bae
AU - A. Halageri
AU - N. Kemnitz
AU - T. Macrina
AU - B. Moya Llamas
AU - A. Schildkamp
AU - M. F. Mazri
AU - J. Ni
AU - R. Roberts
AU - L. Serratosa Capdevila
AU - R. Wang
AU - A. Dsouza
AU - A. Norton
AU - S. Wang
AU - D. Zhang
AU - P. L. Tang
AU - S. Choi
AU - W.-C. A. Lee
AU - D. D. Ginty
PY - 2026
DA - 2026/09/27
PB - bioRxiv
DO - 10.64898/2026.09.27.754843
UR - https://www.biorxiv.org/content/10.64898/2026.09.27.754843v1
AB - 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.
ER -