A novel intracochlear injection method for rapid drug delivery to vestibular end organs.

BACKGROUND: Injection into the inner ear through the round window (RW) or a cochleostomy is a reliable method for delivering drugs or viruses to the cochlea. This method has been less effective for fast deliveries to vestibular end organs. NEW METHOD: We describe a novel approach for rapid delivery of drugs to the vestibular end organ via the oval window (OW) and scala vestibuli in 1-3 month old C57BL/6 mice. The OW was directly accessed through the external ear canal after ablating the tympanic membrane and middle ear ossicles. A canalostomy in the superior canal provided a low pressure point for faster transit of injected solution from the OW to the vestibular neuroepithelia, allowing for higher rates of injection. RESULTS: The efficacy of this technique was shown by fast transit times of a colored artificial perilymph from the OW to the utricle and the ampullae of the horizontal and superior canals in ∼2 min. Following injection, the response of the vestibular nerve was preserved, as measured by the vestibular sensory evoked potentials (VsEP). COMPARISON WITH EXISTING METHODS: Previous studies have used posterior semicircular canals or the RW with canalostomy to gain access to vestibular end organs in mice. The OW with canalostomy, provides the means for high injection rates and fast and reliable delivery of drugs to vestibular hair cells and afferent terminals. CONCLUSIONS: The presented method for injections through the OW provides rapid delivery of solutions to vestibular end organs without adversely affecting vestibular nerve responses measured by VsEP.

Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents.

A group of vestibular afferent nerve fibers with irregular-firing resting discharges are thought to play a prominent role in responses to fast head movements and vestibular plasticity. We show that, in C57BL/6 mice (either sex, 4-5 weeks old), normal activity in the efferent vestibular pathway is required for function of these irregular afferents. Thermal inhibition of efferent fibers results in a profound inhibition of irregular afferents' resting discharges, rendering them inadequate for signaling head movements. In this way, efferent inputs adjust the contribution of the peripheral irregular afferent pathway that plays a critical role in peripheral vestibular signaling and plasticity.SIGNIFICANCE STATEMENT Vestibular end organs in the inner ear receive efferent inputs from the brainstem. Previously, electrical stimulation of efferents was linked to an increase in resting discharges of afferents and a decrease in their sensitivities. Here, we show that localized thermal inhibition of unmyelinated efferents results in a significant decrease in the activity of afferent nerve fibers, particularly those with irregular resting discharges implicated in responses to fast head movements and vestibular compensation. Thus, by upregulating and downregulating of afferent firing, particularly irregular afferents, efferents adjust neural activity sensitive to rapid head movements. These findings support the notion that peripheral vestibular end organs are not passive transducers of head movements and their sensory signal transmission is modulated by efferent inputs.