Evidence that ultrafast non-quantal transmission underlies short-latency vestibular evoked potentials

Abstract Amniotes evolved a unique calyceal postsynaptic terminal in the vestibular organs of the inner ear that underpins quantal and non-quantal transmission at the synapse of sensory hair cells and vestibular afferent neurons. The non-quantal component is of particular interest as it includes an ultrafast synaptic current thought to underlie the exquisite synchronization of action potentials in vestibular afferent fibres to dynamic stimuli such as sound and vibration. Here we demonstrate evidence that non-quantal transmission is responsible for short latency vestibular evoked potentials (vCAPs) in the guinea pig utricle. We first show that, unlike auditory nerve responses which are completely abolished, vCAPs are insensitive to local administration of the AMPA receptor agonist CNQX. Moreover, latency comparisons between presynaptic hair cell and postsynaptic neural responses reveal that the vCAP occurs without measurable synaptic delay. Finally, using a paired-pulse stimulus designed to deplete the readily releasable pool of synaptic vesicles in hair cells, we reveal that forward masking is lacking in vestibular responses, compared to the equivalent cochlear responses. Our data support the hypothesis that the fast component of non-quantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimulation. Significance The mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more pre-synaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of data in the guinea pig that reveal the pre-synaptic transmission of the most sensitive vestibular afferents are faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.