Govindaraju, Aravind ChenrayanQuraishi, Imran H.Lysakowski, AnnaEatock, Ruth AnneRaphael, Robert M.2023-01-272023-01-272023Govindaraju, Aravind Chenrayan, Quraishi, Imran H., Lysakowski, Anna, et al.. "Nonquantal transmission at the vestibular hair cell–calyx synapse: KLV currents modulate fast electrical and slow K+ potentials." <i>Proceedings of the National Academy of Sciences,</i> 120, no. 2 (2023) PNAS: https://doi.org/10.1073/pnas.2207466120.https://hdl.handle.net/1911/114281Vestibular hair cells transmit information about head position and motion across synapses to primary afferent neurons. At some of these synapses, the afferent neuron envelopes the hair cell, forming an enlarged synaptic terminal called a calyx. The vestibular hair cell–calyx synapse supports a mysterious form of electrical transmission that does not involve gap junctions, termed nonquantal transmission (NQT). The NQT mechanism is thought to involve the flow of ions from the presynaptic hair cell to the postsynaptic calyx through low-voltage-activated channels driven by changes in cleft [K+] as K+ exits the hair cell. However, this hypothesis has not been tested with a quantitative model and the possible role of an electrical potential in the cleft has remained speculative. Here, we present a computational model that captures experimental observations of NQT and identifies features that support the existence of an electrical potential (ϕ) in the synaptic cleft. We show that changes in cleft ϕ reduce transmission latency and illustrate the relative contributions of both cleft [K+] and ϕ to the gain and phase of NQT. We further demonstrate that the magnitude and speed of NQT depend on calyx morphology and that increasing calyx height reduces action potential latency in the calyx afferent. These predictions are consistent with the idea that the calyx evolved to enhance NQT and speed up vestibular signals that drive neural circuits controlling gaze, balance, and orientation.engThis article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).Journal articlepnas-2207466120https://doi.org/10.1073/pnas.2207466120