Activation of Central Pattern Generator for Respiration Following Complete High Cervical Spinal Cord Interruption
Abstract
Consistent with the primary goal of the project, we identified the optimal paradigm for epidural stimulation (EDS) todrive paced breathing following complete high cervical (C1) spinal cord injury (SCI) in adult rats. High-frequency EDS ofthe C4 cervical (HF-C4-EDS) segment (the center of the phrenic motor pool and primary spinal inspiratory control) incombination with pharmacological (intrathecal) disinhibition of GABAa- and glycinergic circuits were able to maintainstable paced breathing and diaphragm muscle contraction in transected animals. Application of GABAa and glycine(inhibitory) receptors blockers (GABAzine and strychnine, respectively) in subthreshold concentrations significantlyincreased the tidal volume, amplitude of diaphragm electromyography and phrenic nerve activity in response to HF-C4-EDS. Our anatomical immunohistological studies confirmed a presence of distinctive population of GABAa andglycinergic pre-phrenic interneurons located in III-IX laminas of the spinal cord alongside other pre-phrenicinterneurons. Electrophysiological experiments with Intraspinal single neuron recordings have shown that applicationof GABAzine and strychnine increased spiking frequency in late inspiratory interneurons and motoneurons. Theseneurons could serve as an effective target for HF-C4-EDS and pharmacological neuromodulation for paced breathingfollowing SCI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1070339
Entities
People
- Vitaliy Marchenko
Organizations
- Drexel University