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Functional synaptic connectivity of engrafted spinal cord neurons with hindlimb motor circuitry in the injured spinal cord

Author

Listed:
  • Ashley Tucker

    (Texas A&M University, Department of Biology
    Texas A&M University, Texas A&M Institute for Neuroscience)

  • Angelina Baltazar

    (Texas A&M University, Department of Biology
    Texas A&M University, Department of Biomedical Engineering)

  • Jaclyn T. Eisdorfer

    (Rutgers University, Department of Cell Biology and Neuroscience)

  • Joshua K. Thackray

    (Rutgers University, Department of Cell Biology and Neuroscience)

  • Katie Vo

    (Texas A&M University, Department of Biology)

  • Hannah Thomas

    (Texas A&M University, Department of Biology)

  • Avnika Tandon

    (Texas A&M University, Department of Biology)

  • Joshua Moses

    (Texas A&M University, Department of Biology)

  • Brendan Singletary

    (Texas A&M University, Department of Biology)

  • Tucker Gillespie

    (Texas A&M University, Department of Biology
    Texas A&M University, Department of Animal Science)

  • Ashley Smith

    (Texas A&M University, Department of Biology)

  • Anna Pauken

    (Texas A&M University, Department of Biology)

  • Sneha Nadella

    (Texas A&M University, Department of Biology)

  • Michael Pitonak

    (Texas A&M University, Department of Biology)

  • Sunjay Letchuman

    (Texas A&M University, Department of Biology
    Texas A&M University, Mays Business School)

  • Julius Jang

    (Texas A&M University, Department of Biology)

  • Michael Totty

    (Texas A&M University, Texas A&M Institute for Neuroscience
    Texas A&M University, Department of Psychological and Brain Sciences)

  • Frank L. Jalufka

    (Texas A&M University, Department of Biology)

  • Miriam Aceves

    (Texas A&M University, Department of Biology
    Texas A&M University, Texas A&M Institute for Neuroscience)

  • Andrew F. Adler

    (Novo Nordisk A/S, Cell Therapy, R&ED)

  • Stephen Maren

    (Texas A&M University, Department of Biology
    Texas A&M University, Texas A&M Institute for Neuroscience
    Texas A&M University, Department of Psychological and Brain Sciences
    University of Illinois Urbana-Champaign, Beckman Institute for Advanced Science and Technology)

  • Heath Blackmon

    (Texas A&M University, Department of Biology)

  • Dylan A. McCreedy

    (Texas A&M University, Department of Biology
    Texas A&M University, Texas A&M Institute for Neuroscience
    Texas A&M University, Department of Biomedical Engineering)

  • Victoria Abraira

    (Rutgers University, Department of Cell Biology and Neuroscience)

  • Jennifer N. Dulin

    (Texas A&M University, Department of Biology
    Texas A&M University, Texas A&M Institute for Neuroscience)

Abstract

Spinal cord injury (SCI) results in significant neurological deficits, and curative therapies are lacking. Neural progenitor cell (NPC) transplantation shows promise, as graft-derived neurons (GDNs) can integrate into host spinal cord and support axon regeneration. Here, we examined the synaptic integration of GDNs into hindlimb motor circuits in a mouse thoracic contusion SCI model. Transsynaptic tracing revealed that GDNs form synaptic connections with host motor circuits. Axon mapping showed distinct termination patterns of cholinergic and V2a interneurons within host spinal cord. Chemogenetic activation of GDNs induced muscle activity in a subset of transplanted animals, but NPC transplantation alone did not improve locomotor recovery. These findings indicate that GDNs can integrate into and modulate activity of host circuits, yet limited synaptic connectivity constrains functional recovery. Future studies should enhance graft-host connectivity and refine transplantation strategies to maximize therapeutic benefit for SCI.

Suggested Citation

  • Ashley Tucker & Angelina Baltazar & Jaclyn T. Eisdorfer & Joshua K. Thackray & Katie Vo & Hannah Thomas & Avnika Tandon & Joshua Moses & Brendan Singletary & Tucker Gillespie & Ashley Smith & Anna Pau, 2025. "Functional synaptic connectivity of engrafted spinal cord neurons with hindlimb motor circuitry in the injured spinal cord," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65395-7
    DOI: 10.1038/s41467-025-65395-7
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