Short latency linear vestibular sensory evoked potentials (VsEPs) provide a means to objectively and directly assess the function of gravity receptors in mammals and birds. The importance of this functional measure is illustrated by its use in studies of the genetic basis of vestibular function and disease. Head motion is the stimulus for the VsEP. In the bird, it has been established that neurons mediating the linear VsEP respond collectively to the rate of change in linear acceleration during head movement (i.e. jerk) rather than peak acceleration. The kinematic element of motion responsible for triggering mammalian VsEPs has not been characterized in detail. Here we tested the hypothesis that jerk is the kinematic component of head motion responsible for VsEP characteristics. VsEP amplitudes and latencies changed systematically when peak acceleration level was held constant and jerk level was varied from ~0.9 to 4.6 g/ms. In contrast, responses remained relatively constant when kinematic jerk was held constant and peak acceleration was varied from ~0.9 to 5.5g in mice and ~0.44 to 2.75g in rats. Thus the mammalian VsEP depends on jerk levels and not peak acceleration. We conclude that kinematic jerk is the adequate stimulus for the mammalian VsEP. This sheds light on the behavior of neurons generating the response. The results also provide the basis for standardizing the reporting of stimulus levels, which is key to ensuring that response characteristics reported in the literature by many laboratories can be effectively compared and interpreted.

The mammalian utricular sensory receptors are commonly believed to be non‐spiking cells with electrical activity limited to graded membrane potential changes. Here we provide evidence that during the first post‐natal week, the sensory hair cells of the rat utricle express a tetrodotoxin (TTX)‐sensitive voltage‐gated Na+ current that displays most of the biophysical and pharmacological characteristics of neuronal Na+ current. Single‐cell RT‐PCR reveals that several α‐subunit isoforms of the Na+ channels are co‐expressed within a single hair cell, with a major expression of Nav1.2 and Nav1.6 subunits. In neonatal hair cells, 30 % of the Na+ channels are available for activation at the resting potential. Depolarizing current injections in the range of the transduction currents are able to trigger TTX‐sensitive action potentials. We also provide evidence of a TTX‐sensitive activity‐dependent brain‐derived neurotrophic factor (BDNF) release by early post‐natal utricle explants. Developmental analysis shows that Na+ currents decrease dramatically from post‐natal day 0 (P0) to P8 and become almost undetectable at P21. Concomitantly, depolarizing stimuli fail to induce both action potential and BDNF release at P20. The present findings reveal that vestibular hair cells express neuronal‐like TTX‐sensitive Na+ channels able to generate Na+‐driven action potentials only during the early post‐natal period of development. During the same period an activity‐dependent BDNF secretion by utricular explants has been demonstrated. This could be an important mechanism involved in vestibular sensory system differentiation and synaptogenesis.

Regeneration of synaptic connections between hair cells and spiral ganglion neurons would be required to restore hearing after neural loss. Here we demonstrate by immunohistochemistry the appearance of afferent-like cochlear synapses in vitro after co-culture of de-afferented organ of Corti with spiral ganglion neurons from newborn mice. The glutamatergic synaptic complexes at the ribbon synapse of the inner hair cell contain markers for presynaptic ribbons and postsynaptic densities. We found postsynaptic density protein PSD-95 at the contacts between hair cells and spiral ganglion neurons in newly formed synapses in vitro. The postsynaptic proteins were directly facing the CtBP2-positive presynaptic ribbons of the hair cells. BDNF and NT-3 promoted afferent synaptogenesis in vitro. Direct juxtaposition of the postsynaptic densities with the components of the preexisting ribbon synapse indicated that growing fibers recognized components of the presynaptic sites. Initiation of cochlear synaptogenesis appeared to be influenced by glutamate release from the hair cell ribbons at the presynaptic site since the synaptic regeneration was impaired in glutamate vesicular transporter 3 mutant mice. These insights into cochlear synaptogenesis could be relevant to regenerative approaches for neural loss in the cochlea.