Surgery-free video-oculography in mouse models: enabling quantitative and short-interval longitudinal assessment of vestibular function.

Abstract

Vestibulo-ocular reflex (VOR) responding to acceleration stimuli is originated from the vestibular apparatuses and thus widely used as an in vivo indicator of the vestibular function. We have developed a vestibular function testing (VFT) system that allows to evaluate VOR response with improved efficiency. The previously required surgical procedure has been avoided by using a newly designed animal-immobility setup. The efficacy of our VFT system was demonstrated on the mice with vestibular abnormalities caused by either genetic mutations (Lhfpl5or Cdh23) or applied vestibulotoxicant (3,3'-iminodipropionitrile, IDPN). Daily longitudinal inspection of the VOR response in the IDPN-administered mice gives the first VOR-based daily-progression profile of the vestibular impairment. The capability of VOR in quantifying the severity of toxicant-induced vestibular deficits has been also demonstrated. The acquired VOR-measurement results were validated against the corresponding behavioral-test results. Further validation against immunofluorescence microscopy was applied to the VOR data obtained from the IDPN-administered mice. We conclude that the improved efficiency of our surgery-free VFT system, firstly, enables the characterization of VOR temporal dynamics and quantification of vestibular-impairment severity that may reveal useful information in toxicological and/or pharmaceutical studies; and, secondly, confers our system promising potential to serve as a high-throughput screener for identifying genes and drugs that affect vestibular function.