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Johan Pahlberg, Charles Ratliff, Alapakkam P Sampath; A Role for Release Regularity in Improving Signal Detection at Rod Synapses. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1979. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To signal the detection of a single photon, the rod synapse must remain sensitive to small changes in release rate, yet remain insensitive to random pauses in release that might appear to be photon absorptions. Since channel openings and other events that lead to vesicle fusion are inherently probabilistic, vesicle release is commonly assumed to be random rather than temporally precise. The reliability of photon detection despite the randomness of release is presently unexplained. Our purpose was to investigate the effect of improved regularity of release on signal-to-noise ratio and signal detection at the first retinal synapse.
To characterize synaptic function between rods and rod bipolar cells, we used simulated patterns of vesicle release from a model ribbon, glutamate diffusion through an anatomically-realistic synaptic cleft and model activation of the postsynaptic transduction cascade in bipolar cells. We then recorded rod and rod bipolar cell dark noise with the suction electrode and patch clamp techniques to experimentally compare our model results with physiology.
Our model shows that regular release can improve synaptic signaling at the rod synapse. We find that local release inhibition can drive phase synchronization among ribbon release sites, which regularizes release and steadies the concentration of cleft glutamate in darkness. Our patch clamp recordings of mouse rod inner segments show small oscillations in dark noise, and we propose that this may be an indication of local release inhibition. These oscillations could not be attributed to phototransduction, and were not evident in recordings of rod bipolar cells in darkness. To isolate the mechanism(s) responsible for the observed oscillations, we applied a series of blockers known to affect inner segment properties. Our results indicate oscillations are unlikely to originate from Group III metabotropic glutamate receptors, L-type Ca2+channels, or horizontal cell feedback.
Release inhibition can induce regular release from rods to ON-BCs to suppress fluctuations in release rate that would cause false-positive photon detection near visual threshold, and thus improves signal-to-noise ratio and signal transfer at the first retinal synapse. The inner segment mechanisms of release inhibition, such as the role of inner segment conductances, Zn+ and proton block or lateral movement of Ca2+ channels are under investigation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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