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Increasing the excitability of V2a neurons restores diaphragm function following spinal cord injury
Author(s) -
JENSEN VICTORIA N,
Alilain Warren,
Crone Steven A
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.731.1
Subject(s) - spinal cord injury , spinal cord , medicine , respiratory center , diaphragm (acoustics) , brainstem , motor neuron , neuron , anesthesia , cord , neuroscience , anatomy , respiratory system , biology , surgery , physics , acoustics , loudspeaker
We hypothesize that ipsilaterally projecting glutamatergic V2a neurons in the ventral spinal cord and brainstem contribute to recovery of diaphragm function following injury. To test our hypothesis, we used a transgenic mouse line that expresses DREADDs in V2a neurons in order to increase their excitability via activation of G q signaling pathways following injection of the drug‐like molecule clozapine‐N‐oxide (CNO). We performed a high level C2 hemisection (C2Hx) spinal cord injury to paralyze the diaphragm ipsilateral to injury. Electromyography (EMG) recordings of the ipsilateral diaphragm confirmed paralysis. However, increasing V2a neuron excitability by intraperitoneal injection of CNO restored rhythmic burst activity to the paralyzed diaphragm within hours or days after injury. Moreover, the contralateral (uninjured side) diaphragm is able to maintain regular rhythmic breathing when V2a neuron activity is altered. These results indicate that targeting Gq signaling pathways in V2a neurons has the potential to restore function to respiratory muscles following spinal cord injury without significant adverse side effects on respiratory rhythm generation. Support or Funding Information UK Center for Clinical and Translational Science, Cincinnati Children's Hospital Medical Center Division of Neurosurgery, Albert J. Ryan Fellowship, University of Cincinnati Neuroscience Graduate Program This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .