Properties of multivesicular release from mouse rod photoreceptors support transmission of single-photon responses

Abstract

Vision under starlight requires rod photoreceptors transduce and transmit single photon responses to the visual system. Small single photon voltage changes must therefore cause detectable reductions in glutamate release. We found that rods achieve this by employing mechanisms that enhance release regularity and its sensitivity to small voltage changes. At the resting membrane potential in darkness, mouse rods exhibit coordinated and regularly timed multivesicular release events, each consisting of ~17 vesicles and occurring 2-3 times more regularly than predicted by Poisson statistics. Hyperpolarizing rods to mimic the voltage change produced by a single photon abruptly reduced the probability of multivesicular release nearly to zero with a rebound increase at stimulus offset. Simulations of these release dynamics indicate that this regularly timed, multivesicular release promotes transmission of single photon responses to post-synaptic rod bipolar cells. Furthermore, the mechanism is efficient, requiring lower overall release rates than uniquantal release governed by Poisson statistics.

Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells

“…Assuming the light-evoked responses were made up of a linear supposition of quantal events, we estimate the peak instantaneous release rate to be 5-10 vesicles/s, which is in line with previous in vivo estimates made in zebrafish BC terminals (James et al, 2021(James et al, , 2019. We also estimated the steady-state release rates to be ~ 3 vesicles/s at proximal sites and ~1 vesicle/s at distal sites, which is well below the maximum release rate estimated for photoreceptor synapses, which also contain ribbons (Hays et al, 2021(Hays et al, , 2020.…”

Eliminating Synaptic Ribbons from Rods and Cones Halves the Releasable Vesicle Pool and Slows Down Replenishment

“…When rods are voltage-clamped at their typical resting potential in darkness of −40 mV, we observed bursts of multiquantal release that occurred at semiregular intervals [ 35 , 36 ]. The size and regularity of these multiquantal release events may help rod bipolar cells discriminate single photon responses during an ongoing release from rods [ 35 ].…”

“…When rods are voltage-clamped at their typical resting potential in darkness of −40 mV, we observed bursts of multiquantal release that occurred at semiregular intervals [ 35 , 36 ]. The size and regularity of these multiquantal release events may help rod bipolar cells discriminate single photon responses during an ongoing release from rods [ 35 ]. As illustrated in Figure 9 , regular and periodic multiquantal release events remained in the rods lacking ribbons, but the duration of each multiquantal event was halved in the rod Ribeye CKO mice ( Figure 9 ; p = 0.003, nested t -test, n = 10 control rods, 167 events; n = 5 rod Ribeye CKO rods, 98 events).…”

“…These release events are not tightly synchronized with one another, but instead involve the sequential release of multiple vesicles with each event thought to empty the RRP [ 36 ]. The size and regularity of these release events can improve the ability of rod bipolar cells to detect and distinguish changes in release produced by small single photon voltage responses in rods [ 35 ]. It has been proposed that descent down the ribbon could provide a mechanism for regularizing release [ 49 ].…”

“…Loss of ribbons from rods and cones also halved scotopic and photopic ERG b-waves, halved the RRP, and slowed down vesicle replenishment. Loss of ribbons also shortened multiquantal release events that may help encode visual information at visual threshold [ 35 , 36 ]. Our results suggest that by expanding the RRP and speeding up replenishment, rod and cone ribbons can play an important role in improving visual performance.…”