Paper Title
KCNQ4 Potassium Channel Subunit Deletion and Startle Reflex

Abstract
The KCNQ4 ion channel subunit forms channels responsible for M-current, a muscarine-sensitive potassium current regulating neuronal excitability. In contrast with other KCNQ subunits, its expression is restricted to the cochlear outer hair cells, the auditory brainstem and other brainstem nuclei greatly overlapping with structures involved in startle reflex. Although it can be expected that startle reflex is affected by the loss of KCNQ4 channel, the alteration of this reflex has not been documented. To achieve this aim, young adult KCNQ4 knockout mice and wild type littermates were used for testing acoustic startle. The acoustic startle reflex was exaggerated on knockout mice compared to wild type ones. In the next experiment, we involved mice expressing hM3D in the pontine caudal nucleus and neurons innervating it as a model of hyperexcitability in nuclei involved in startle. A similar increase of the first acoustic startle amplitude was demonstrated with an increased habituation of the reflex. We found that the acoustic startle reflex is exaggerated and minimal habituation occurs in KCNQ4 knockout animals. These changes are distinct from the effects of the hyperexcitability of nuclei involved in startle. One can conclude that the exaggerated startle reflex found with the KCNQ4 subunit deletion is the consequence of both the cochlear damage and the changes in neuronal excitability of startle networks.