Efferent Inputs Are Required for Normal Function of Vestibular Nerve Afferents

Abstract

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.

Cholinergic Modulation of Membrane Properties of Calyx Terminals in the Vestibular Periphery

“…We have recently shown that inhibition of efferents results in a decrease in resting discharge of afferents and even complete shutdown of the most irregular afferents [54]. The present study supports these previous findings.…”

“…Similar results were observed with application of KCNQ antagonist linopirdine dihydrochloride. Our findings suggest that without mAChR activity, calyces cannot respond to stimuli due to open KCNQ channels and the resultant high spike frequency adaptation, a finding supported by our previous in vivo findings [54]. We propose that through activation of mAChRs, cholinergic efferent inputs provide the means for changing membrane properties of calyx terminals and consequently, spontaneous activity and response properties of irregular afferents.…”

The mammalian efferent vestibular system utilizes cholinergic mechanisms to excite primary vestibular afferents

“…Spontaneous activity in vestibular efferents is documented in frog, fish and mammals 40 – 44 . Furthermore, recent data 45 has suggested spontaneous activity in mouse EVS neurons augments vestibular afferent discharge, perhaps through continuous activation of the same peripheral mechanisms driving efferent-mediated slow excitation in our study. To assess whether EVS neurons were active in our preparation, we asked if the same rostrocaudal sectioning altered afferent baseline discharge.…”

“…Furthermore, different general anaesthetics are associated with varying decreases in efferent activity in vestibular, auditory, and lateral line systems 62 – 65 . Differences in spontaneous EVS activity here and Raghu et al 45 could be related to use of urethane versus ketamine anaesthesia. Further studies regarding anaesthetic effects on mammalian EVS function are warranted.…”

“…Were such activity to release ACh and activate mAChRs driving efferent-mediated slow excitation, it could elevate afferent background discharge. Support for this idea comes from a study suggesting photothermal stimulation in anesthetized mice inhibits EVS neurons and reduces afferent activity 45 . However, in our preparation, we were unable to demonstrate a role for spontaneous efferent activity as neither severing EVS neurons nor IB mAChR blockade with scopolamine or atropine had significant effects on afferent background discharge.…”