title: Transmitter release in inner hair cell synapses: a model analysis of spontaneous and driven rate properties of cochlear nerve fibres.
abstract: The inner hair cell (IHC) synapse is one of the stages of cochlear processing that determine the relation between sound pressure level and spike rate in auditory nerve fibres. Transmitter released in the non-stimulated condition is held responsible for the wide range of spontaneous spike rates (SR) observed in these fibres. Properties of stimulated spike activity in auditory nerve fibres, including rate threshold and operating range of a fibre, are known to systematically vary with SR. This paper presents a model analysis of the relation between IHC transmembrane potential and transmitter release rate as becoming manifest in these spontaneous and driven rate properties. A previously developed computational model is used to identify those transfer properties of its synapse section which lead to reproduction of the variation of rate thresholds, shapes of rate-intensity functions and maximal driven rate with SR known from the literature. First a simple additive release model, in which driven transmitter release depends linearly on IHC potential, is elaborated. Its results lead to the hypothesis that the true release function is non-linear and variable across synapses generating different SR. An exponential release function is then introduced, with parameters varying across SR in a physiologically dictated way. This approach leads to adequate reproduction of the variation in rate thresholds and rate-intensity functions with SR. Finally, the model is applied in an inverse way to directly estimate the release function from given rate-intensity functions. The conclusion of both forward and inverse model analyses is that transmitter release is a non-linear function of IHC potential which, by the systematic variation of its parameters across SR, effectively leads to the physiological variation in dynamic range across fibres of different SR. Possible relations of these results with ultrastructural morphology and basic physiology of IHC synapses are discussed.
authors.affiliation: Leiden University Hospital, Department of ENT/Audiology, The Netherlands. r.schoonhoven@ent.medfac.leidenuniv.nl
authors.forename: R
authors.initials: R
authors.lastname: Schoonhoven
authors.forename: V F
authors.initials: VF
authors.lastname: Prijs
authors.forename: J H
authors.initials: JH
authors.lastname: Frijns
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D003051:Cochlea / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000502:physiology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D008959:Models, Neurological; D009412:Nerve Fibers / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D000159:Vestibulocochlear Nerve / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents