Mechanism of High-Frequency Signaling at a Depressing Ribbon Synapse

Ribbon synapses mediate continuous release in neurons that have graded voltage responses. While mammalian retinas can signal visual flicker at 80–100 Hz, the time constant, τ, for the refilling of a depleted vesicle release pool at cone photoreceptor ribbons is 0.7–1.1 s. Due to this prolonged depression, the mechanism for encoding high temporal frequencies is unclear. To determine the mechanism of high-frequency signaling, we focused on an “Off” cone bipolar cell type in the ground squirrel, the cb2, whose transient postsynaptic responses recovered following presynaptic depletion with a τ of ∼0.1 s, or 7- to 10-fold faster than the τ for presynaptic pool refilling. The difference in recovery time course is caused by AMPA receptor saturation, where partial refilling of the presynaptic pool is sufficient for a full postsynaptic response. By limiting the dynamic range of the synapse, receptor saturation counteracts ribbon depression to produce rapid recovery and facilitate high-frequency signaling. •Vesicle docking sites at cone ribbons are slowly refilled following release•Slow vesicle refilling is expected to limit high temporal frequency signaling•Cones make high gain, readily saturating synapses with cb2 “Off” bipolar cells•High gain and saturation hasten synapse recovery to enable high-frequency signaling At ribbon synapses, the rate of vesicle turnover at membrane docking sites limits high-frequency transmission. Grabner et al. identify a postsynaptic mechanism at a cone-to-“Off” bipolar cell synapse that counteracts slow turnover to enhance high-frequency signaling.