| Popis: |
Vestibular research currently relies on single response measures such as ex vivo hair cell and in vivo single unit recordings. Although these methods allow detailed insight into the response properties of individual vestibular hair cells and neurons, they do not provide a holistic understanding of peripheral vestibular functioning and its relationship to vestibular pathology in a living system. For this to take place, in vivo recordings of peripheral vestibular nerve, hair cell and mechanical function are needed. The previous inability to record vestibular hair cell responses stemmed from a difficulty in accessing the vestibular end-organs and stimulating them in isolation of the cochlea. To circumvent this, we developed a ventral surgical approach, removing the cochlea, to provide full access to the basal surface of the utricular macula. This allowed functional and mechanical utricular hair cell recordings, alongside gross utricular nerve responses. Recordings were performed in anaesthetized guinea pigs using Bone Conducted Vibration (BCV) and Air Conducted Sound (ACS) stimuli, providing a clinical link to vestibular reflex testing. We have thus far performed experiments involving: 1) Selective manipulation of vestibular nerve function, using electrical stimulation of the central vestibular system. 2) Glass micropipette recordings from the basal surface of the macular epithelium, which provided a robust and localized measure of extracellular utricular hair cell function. 3) With the macular exposed, we have measured the dynamic motion of the macula using Laser Doppler Vibrometry, which was recorded alongside the hair cell and nerve response recordings. 4) We have used physiological and pharmacological experimental manipulations to selectively modulate utricular nerve, hair cell or mechanical function, demonstrating the ability to differentially diagnose the basis of peripheral vestibular disorders in the mammalian utricle. These tools allow for a more complete understanding of peripheral vestibular function and a first order perspective into clinical disorders effecting the otoliths. |
