TY - JOUR
T1 - Comprehensive Monosynaptic Rabies Virus Mapping of Host Connectivity with Neural Progenitor Grafts after Spinal Cord Injury
AU - Adler, Andrew F.
AU - Lee-Kubli, Corinne
AU - Kumamaru, Hiromi
AU - Kadoya, Ken
AU - Tuszynski, Mark H.
N1 - Funding Information:
We thank E. Staufenberg, B. Durham, S. Im, G. Poplawski, J. Dulin, L. Graham, J. Weber, S. Ceto, J. Connor, P. Lu, and D. Gibbs for technical assistance. This work was supported by the Veterans Administration (Gordon Mansfield Spinal Cord Injury Consortium), the Craig H. Neilsen Foundation, the Bernard and Anne Spitzer Charitable Trust, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Grants-in-Aid for Scientific Research, and the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2017 The Authors
PY - 2017/6/6
Y1 - 2017/6/6
N2 - Neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. Mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. Using transgenic mouse spinal neural progenitor cell grafts expressing the TVA and G-protein components of the modified rabies virus system, we initiated monosynaptic tracing strictly from graft neurons placed in sites of cervical spinal cord injury. We find that graft neurons receive synaptic inputs from virtually every known host system that normally innervates the spinal cord, including numerous cortical, brainstem, spinal cord, and dorsal root ganglia inputs. Thus, implanted neural progenitor cells receive an extensive range of host neural inputs to the injury site, potentially enabling functional restoration across multiple systems.
AB - Neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. Mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. Using transgenic mouse spinal neural progenitor cell grafts expressing the TVA and G-protein components of the modified rabies virus system, we initiated monosynaptic tracing strictly from graft neurons placed in sites of cervical spinal cord injury. We find that graft neurons receive synaptic inputs from virtually every known host system that normally innervates the spinal cord, including numerous cortical, brainstem, spinal cord, and dorsal root ganglia inputs. Thus, implanted neural progenitor cells receive an extensive range of host neural inputs to the injury site, potentially enabling functional restoration across multiple systems.
UR - http://www.scopus.com/inward/record.url?scp=85018939204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018939204&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2017.04.004
DO - 10.1016/j.stemcr.2017.04.004
M3 - Article
C2 - 28479302
AN - SCOPUS:85018939204
VL - 8
SP - 1525
EP - 1533
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 6
ER -