Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission
Annual rept. 1 Nov 2013-31 Oct 2014
WISCONSIN UNIV MADISON
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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 NKCC1KCC2 balance in phrenic motor neurons, thereby degrading CSC and restoring rAIH chloride-dependent synaptic inhibition. Tissues were collected for immunocytochemistry and surface biotinylationWestern 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 KCC2NKCC1 balance may be reversed in the injured versus noninjured spinal cord. In the next year, we plan to complete electrophysiology and immunohistochemicalWestern blot analyses, prepare a manuscript for publication and begin work on Specific Aims 1c, 1d, 2c.
- Anatomy and Physiology
- Medicine and Medical Research