Functional synaptic connectivity of engrafted spinal cord neurons with hindlimb motor circuitry in the injured spinal cord
Year: 2025
Type: article
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. Neural progenitor cell transplantation shows promise for treating spinal cord injury. However, here, the authors show that graft-derived neurons form limited synaptic connections with host spinal motor circuits after injury, constraining functional motor recovery.
Source: Nature Communications
Authors: 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 Pauken, Sneha Nadella, Michael Pitonak, Sunjay Letchuman, Julius Jang, Michael Totty, Frank L. Jalufka, Miriam Aceves, Andrew F. Adler, Stephen Maren, Heath Blackmon, Dylan A. McCreedy, Victoria Abraira, Jennifer N. Dulin
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Paralyzed Veterans of America Research Foundation, Paralyzed Veterans of America, Wings for Life, National Institutes of Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: Dissecting Connectivity and Function of Transplanted Interneurons in the Injured Spinal Cord, G2144664386, G465530944, G5134678249, A new mechanistic and technological framework for uncovering the spinal cord neural systems important for functional recovery after injury, G8380376465, G9000079167, G9000154996, G9000167090, L-selectin shedding as a novel therapeutic strategy to mitigate acute secondary damage after spinal cord injury
OpenAlex ID: W4416590192