Faculty Collaboration Database

Cervical excitatory neurons sustain breathing after spinal cord injury. Nature 2018 Oct;562(7727):419-422

Date

10/12/2018

Pubmed ID

30305735

DOI

10.1038/s41586-018-0595-z

Scopus ID

2-s2.0-85055018424 (requires institutional sign-in at Scopus site)   50 Citations

Abstract

Dysfunctional breathing is the main cause of morbidity and mortality after traumatic injury of the cervical spinal cord^1,2 and often necessitates assisted ventilation, thus stressing the need to develop strategies to restore breathing. Cervical interneurons that form synapses on phrenic motor neurons, which control the main inspiratory muscle, can modulate phrenic motor output and diaphragmatic function^3-5. Here, using a combination of pharmacogenetics and respiratory physiology assays in different models of spinal cord injury, we show that mid-cervical excitatory interneurons are essential for the maintenance of breathing in mice with non-traumatic cervical spinal cord injury, and are also crucial for promoting respiratory recovery after traumatic spinal cord injury. Although these interneurons are not necessary for breathing under normal conditions, their stimulation in non-injured animals enhances inspiratory amplitude. Immediately after spinal cord injury, pharmacogenetic stimulation of cervical excitatory interneurons restores respiratory motor function. Overall, our results demonstrate a strategy to restore breathing after central nervous system trauma by targeting a neuronal subpopulation.

Author List

Satkunendrarajah K, Karadimas SK, Laliberte AM, Montandon G, Fehlings MG

Author

Kajana Satkunendrarajah PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Diaphragm
Female
Inhalation
Interneurons
Mice
Motor Neurons
Respiration
Spinal Cord Injuries