Presynaptic Ca_V1.3 Channels Regulate Synaptic Ribbon Size and Are Required for Synaptic Maintenance in Sensory Hair Cells

Abstract

L-type calcium channels (CaV1) are involved in diverse processes, such as neurotransmission, hormone secretion, muscle contraction, and gene expression. In this study, we uncover a role for CaV1.3a in regulating the architecture of a cellular structure, the ribbon synapse, in developing zebrafish sensory hair cells. By combining in vivo calcium imaging with confocal and super-resolution structured illumination microscopy, we found that genetic disruption or acute block of CaV1.3a channels led to enlargement of synaptic ribbons in hair cells. Conversely, activating channels reduced both synaptic-ribbon size and the number of intact synapses. Along with enlarged presynaptic ribbons in caV1.3a mutants, we observed a profound loss of juxtaposition between presynaptic and postsynaptic components. These synaptic defects are not attributable to loss of neurotransmission, because vglut3 mutants lacking neurotransmitter release develop relatively normal hair-cell synapses. Moreover, regulation of synaptic-ribbon size by Ca2+ influx may be used by other cell types, because we observed similar pharmacological effects on pinealocyte synaptic ribbons. Our results indicate that Ca2+ influx through CaV1.3 fine tunes synaptic ribbon size during hair-cell maturation and that CaV1.3 is required for synaptic maintenance.

Dynamics of cochlear synaptopathy after acoustic overexposure

“…Given that the sizes of these puncta are really measures of staining intensity (which should be proportional to numbers of clustered molecules), it makes sense that fibers with high thresholds (modiolar side) should have smaller gluR patches. The reason for the larger ribbons is less obvious; however, prior study in zebrafish lateral line suggests that ribbon size is dynamically regulated by negative feedback from calcium entry at the synapse (Sheets et al 2012). Thus, a less active (low-SR) synapse would be expected to have a larger ribbon in the normal ear, as appears to the case (Fig.…”

Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish

“…Hair cells specialized for high-frequency stimuli have a greater number of vesicles and calcium currents (Obholzer et al 2008;Schnee et al 2005;Sheets et al 2012;Trapani et al 2009). They also have a greater ease of vesicle release, a faster recycling of vesicles and more efficient docking (Fuchs et al 2003;Khimich et al 2005;Moser et al 2006;Schnee et al 2005).…”

Olivocochlear Innervation Maintains the Normal Modiolar-Pillar and Habenular-Cuticular Gradients in Cochlear Synaptic Morphology

“…In zebrafish lateral line hair cells, ribbon size is controlled by negative feedback from Ca ++ entry through presynaptic, voltage-gated Ca ++ channels (Sheets et al 2012). If low SR synapses have fewer Ca ++ channels, then presynaptic ribbons would be larger, if the same feedback system is present.…”