Philippe Vincent, Didier Dulon et al. dans Cell Reports

Philippe Vincent 1er auteur est  en post-doc à l’Université Johns Hopkins (School of Medicine, Baltimore). Didier Dulon: Equipe Neurophysiologie de la Synapse Auditive, Inserm U1120, 33076 Bordeaux, France, Université de Bordeaux, Bordeaux Neurocampus

Our study shows that proton (H+) release during synaptic exocytosis of glutamatergic vesicles produces a fast transient block of presynaptic Ca2+ currents (ICaTB) at auditory hair cell ribbon synapses. This ICaTB requires a compact organization of the Cav1.3 Ca2+ channels at the hair cell active zone. This process involves a synchronized multivesicular release (MVR) of glutamatergic synaptic vesicles that produces an efficient acidification of the synaptic cleft near the presynaptic Ca2+ channels.

ICaTB is not observed in central neuronal synapses such as the auditory synapse of the calyx of Held where Ca2+ channels, although organized in nanodomains near the sites of release, constitute several topographically dispersed clusters with a rather large inter-cluster distance. ICaTB appears as a specific property of ribbon synapses. Furthermore, our results show that MVR and ICaTB in hair cells is orchestrated by the multi-C2 Ca2+ sensor otoferlin.

We propose that ICaTB acts as a fast feedback mechanism that controls transmitter release at auditory hair cell ribbon synapses and therefore contributes to the fast in vivo spike adaptation of the auditory afferent nerve fibers, an essential property for intensity-frequency coding and fast sound localization.  (below, click  on the picture to enlarge…)