Vaithianathan, T., Zanazzi, G., Henry, D., Akmentin, W., and Matthews, G. (2013) Stabilization of spontaneous neurotransmitter release at ribbon synapses by ribbon-specific subtypes of complexin. The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(19):8216-8226.
Ribbon synapses of tonically releasing sensory neurons must provide a large pool of releasable vesicles for sustained release,
while minimizing spontaneous release in the absence of stimulation. Complexins are presynaptic proteins that may accomplish
this dual task at conventional synapses by interacting with the molecular machinery of synaptic vesicle fusion at the active
zone to retard spontaneous vesicle exocytosis yet facilitate release evoked by depolarization. However, ribbon synapses of
photoreceptor cells and bipolar neurons in the retina express distinct complexin subtypes, perhaps reflecting the special
requirements of these synapses for tonic release. To investigate the role of ribbon-specific complexins in transmitter release,
we combined presynaptic voltage clamp, fluorescence imaging, electron microscopy, and behavioral assays of photoreceptive
function in zebrafish. Acute interference with complexin function using a peptide derived from the SNARE-binding domain increased
spontaneous synaptic vesicle fusion at ribbon synapses of retinal bipolar neurons without affecting release triggered by depolarization.
Knockdown of complexin by injection of an antisense morpholino into zebrafish embryos prevented photoreceptor-driven migration
of pigment in skin melanophores and caused the pigment distribution to remain in the dark-adapted state even when embryos
were exposed to light. This suggests that loss of complexin function elevated spontaneous release in illuminated photoreceptors
sufficiently to mimic the higher release rate normally associated with darkness, thus interfering with visual signaling. We
conclude that visual system-specific complexins are required for proper illumination-dependent modulation of the rate of neurotransmitter
release at visual system ribbon synapses.