Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission
Abstract
Our fundamental goal is to test the hypothesis that spontaneous and induced plasticity in chloride-dependent synaptic inhibition of phrenic motor neurons contributes to functional recovery from chronic cervical spinal contusion (CSC) injuries. In the last two years, we performed experiments to test the hypothesis that CSC and repetitive acute intermittent hypoxia (rAIH) shift the NKCC1/KCC2 balance in phrenic motor neurons, degrading (CSC) and restoring (rAIH) chloride-dependent synaptic inhibition, and began experiments investigating the role of spinal PKCxi in spontaneous recovery of breathing following CSC. Our analyses indicate that CSC increases membrane NKCC1, and decreases the membrane-cytosol KCC2 ratio, consistent with the interpretation that compensatory shifts in NKCC1/KCC2 balance in phrenic motor neurons preserves respiratory function following CSC. rAIH had no apparent effects on either protein. Preliminary studies also suggest that spontaneous recovery of diaphragm EMG and breathing capacity occurs within the first 3 days following injury by a spinal PKCxi-dependent mechanism. In the final months of this no cost extension, we plan to: 1) prepare a manuscript for publication concerning immunofluorescence results, and 2) complete experiments concerning the role of PKCxi in spontaneous ventilatory compensation in unanesthetized rats.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1011676
Entities
People
- Gordon S. Mitchell
- Tracy Baker-herman
Organizations
- University of Wisconsin System