Date of Award

2020

Degree Type

Thesis

Degree Name

Master of Science in Interdisciplinary Neurosciences

Department

Interdisciplinary Studies

First Advisor

Katharina Quinlan

Abstract

Cerebral palsy (CP) is caused by a variety of factors attributed to early brain damage, resulting in permanently impaired motor control, marked by weakness and muscle stiffness. To find out if altered physiology of spinal motoneurons (MNs) could contribute to movement deficits, we performed whole cell patch clamp in neonatal rabbit spinal cord slices after developmental injury at 79% gestation. After preterm hypoxia-ischemia (HI), rabbits are born with motor deficits consistent with a spastic phenotype including hypertonia and hyperreflexia. There is a range in severity, thus kits are classified as severely affected, mildly affected, or unaffected based on modified Ashworth scores and other behavioral tests. At postnatal day (P)0-5, we recorded electrophysiological parameters of 40 MNs in transverse spinal cord slices using whole cell patch clamp. We found significant differences between groups (severe, mild, unaffected and sham control MNs). Severe HI MNs showed more sustained firing patterns, depolarized resting membrane potential, and fired action potentials at a higher frequency. In addition, HI cells also showed alteration in their ability to modulate their firing rates to sustained input. These properties could contribute to muscle stiffness and weakness, which are hallmarks of spastic CP. In summary, these changes we observed in spinal MN physiology likely contribute to the commonly observed phenotype in CP, and therapeutic strategies could target excitability of spinal MNs.

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