Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission
Abstract
The fundamental goal of our proposal 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 injuries. In the last year, we performed experiments to test the specific hypothesis that cervical spinal contusion injuries (CSC) and repetitive acute intermittent hypoxia (rAIH) shift the NKCC1/KCC2 balance in phrenic motor neurons, thereby degrading (CSC) and restoring (rAIH) chloride-dependent synaptic inhibition. Tissues were collected for immunocytochemistry and surface biotinylation/Western blot analysis and electrophysiology was performed on rats with sham surgery or CSC with and without AIH. We project that all tissues will be collected and all electrophysiological data will be obtained by December 12, 2014 for studies related to Specific Aims 1a, 1b, 2a, 2b. Our preliminary data suggest that membrane expression of KCC2 is reduced following CSC, which is normalized by rAIH treatment. Our data further suggest the surprising finding that rAIH effects on KCC2/NKCC1 balance may be reversed in the injured versus noninjured spinal cord. In the next year, we plan to complete electrophysiology and immunohistochemical/Western blot analyses, prepare a manuscript for publication and begin work on Specific Aims 1c, 1d, 2c.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 27, 2014
- Accession Number
- ADA624259
Entities
People
- Gordon S. Mitchell
- Tracy Baker-herman
Organizations
- University of Wisconsin–Madison