Timothy Cope (Committee Member), Robert Fyffe (Advisor), Robert Putnam (Committee Member)
Master of Science (MS)
Peripheral axotomy causes significant alterations in intrinsic motoneuron activity and excitability. Despite successful reinnervation of peripheral targets after injury, the recovery of motor function is incomplete. Following axotomy in the adult cat, there is an increase in the afterhyperpolarization (AHP) of the action potential in specific motoneuron types. AHP duration can be inversely correlated with the amount of Ih or sag current and further shaped through SK (Small conductance calcium-activated potassium) channel currents (Gustafsson and Pinter, 1985; Kuno, Miyata, and Muñoz-Martinez, 1974a). Hyperpolarizing-cyclic nucleotide gated (HCN) channels underlie sag currents and are critical to neuronal function by their unique property of a reverse voltage-dependence that leads to activation upon hyperpolarization. There are four isoforms of HCN channels, one of which, HCN1, is expressed in motoneurons. Because there is an increase in AHP after injury, we hypothesize that there will be a decrease in expression of HCN1 immunoreactivity (IR) in the medial and lateral gastrocnemius (MG/LG) α-motoneurons following tibial nerve axotomy. To test this hypothesis, we used immunohistochemical approaches in two in vivo injury models, namely the tibial nerve crush model, that permits peripheral reinnervation of the peripheral targets and the tibial nerve ligation model, that prevents peripheral reinnervation from occurring, thus allowing us to distinguish between mechanisms and their dependency on proper reinnervation of peripheral targets. Lumbar spinal cord tissue was analyzed using immunohistochemical techniques to identify retrogradely labeled, injured MG/LG α-motoneurons and HCN1- IR. These data suggest that following injury there is a decrease in HCN1-IR followed by a peripheral reinnervation-dependent recovery.
Department or Program
Department of Neuroscience, Cell Biology & Physiology
Year Degree Awarded
Copyright 2012, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.