A synaptic wiring diagram underlying modality-specific ascending pathways of the superficial spinal dorsal horn
Year: 2026
Type: preprint
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.
Authors: Wangchu Xiang, Ramin Khajeh, Kevin Delgado, Jingyi Liu, Adrian Holtrup, Qiyu Zhang, Sidrick Cameron, Tri Nguyen, J. Alex Bae, Akhilesh Halageri, Nico Kemnitz, Thomas Macrina, Borja Moya Llamas, Alice Schildkamp, Mohd Freezely Mazri, Julianne Ni, Ruairi Roberts, Laia Serratosa Capdevila, Ruoming Wang, Amelia Dsouza, Aliya Norton, Songyang Wang, Dong Zhang, Paul Lindu Tang, Seungwon Choi, Wei-Chung Allen Lee, David D. Ginty
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7215120219