HCN1 Immunoreactivity of α‐motoneurons Following Peripheral Nerve Injury

Abstract

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 cat, there is an increase in the Afterhyperpolarization (AHP) of the action potential (Gustaffson and Pinter, 1983). AHP duration can be inversely correlated with the amount Ih or sag current and further shaped through SK currents. 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 with only HCN1 being observed post-synaptically 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) a-motoneurons following tibial neve axotomy. To test this hypothesis, we used two in vivo injury models. The tibial nerve crush model will allow peripheral reinnervation of the peripheral targets and the tibial nerve cut and ligation model prevents peripheral reinnervation from occurring, thus allowing us to distinguish between mechanisms that may or may not be dependent proper reinnervation of peripheral targets. Spinal cord tissue was analyzed using immunohistochemical techniques to identify retrogradely labeled MG/LG alpha motoneurons and HCN1-IR. These data suggest that following injury there is a decrease in HCN1-IR followed by a recovery in HCN1-IR after peripheral reinnvervation.