Logo image
Back
Cholinergic V0c spinal interneurons and respiratory plasticity after cervical spinal cord injury
Dissertation

Cholinergic V0c spinal interneurons and respiratory plasticity after cervical spinal cord injury

Kayla Anne Schardien
Doctor of Philosophy (Ph.D.), Drexel University
Nov 2024
DOI:
https://doi.org/10.17918/00010799
pdf
Schardien_Kayla_20249.15 MB
PDF Embargoed Access, Embargo ends: 31 Jan 2027

Abstract

Spinal cord--Wounds and injuries Activity-based therapies Intermittent hypoxia training Pitx2-V0c Interneurons Respiration Spinal interneurons
Spinal cord injury (SCI) often leads to debilitating loss of function, with about 60% of cases affecting the cervical level, which results in life-threatening respiratory impairments. However, spontaneous plasticity can lead to partial recovery, driven in part by spinal interneurons that alter their function and connectivity to form new pathways. Activity-based therapies such as intermittent hypoxia (IH) respiratory training enhance this plasticity. This study examines the role of V0c spinal interneurons in respiratory plasticity after high cervical SCI in mice. While V0c interneurons have a prominent role in locomotor circuits, their contributions to phrenic motor function remain unclear. Using a transgenic mouse model, we aim to understand this limited recovery and test treatments that can enhance it, focusing on whether V0c interneurons might represent a key therapeutic target for improving recovery after SCI. Adult mice received a unilateral hemisection at the second cervical segment (C2), denervating the phrenic motor circuit controlling the diaphragm. A subset of those mice underwent IH respiratory training. A transsynaptic retrograde tracer was applied to the ipsilateral hemidiaphragm to label phrenic motoneurons and spinal interneurons, and diaphragm activity was measured via electromyography. Our anatomical and functional data suggest that V0c interneurons are involved in respiratory recovery following SCI in a more limited capacity than with locomotion. These findings underscore the need to focus on alternative pathways for respiratory recovery. Understanding changes in interneuronal circuitry after injury and post-rehabilitative strategies remains an invaluable opportunity to drive research investigations.

Metrics

10 Record Views

Details

Logo image