Design of the mammalian cone photoreceptor to Off bipolar cell synapse

Graded synapses in sensory systems reliably transmit small signals in the presence of continuous quantal noise. To understand how signaling is optimized during graded transmission, we counted the number of vesicles released by a mammalian cone terminal and compared it to the simultaneous responses in each Off bipolar cell type. Off bipolar cells contacting the terminal base comprised two groups depending on how they sampled transmitter release. In both groups, responses initially grew non-linearly with the number of released vesicles implicating a role for cooperativity during sparse release. One group sampled release from most of a cone’s ∼20 ribbons and can exploit averaging to improve signal reliability. The other, less-sensitive group made 1-3 contacts at the terminal center and responded to pooled transmitter, a consequence of membrane depolarization, using an insensitive kainate receptor. Off bipolar cells use different strategies to minimize transmission noise and encode cone output over different ranges. ### Competing Interest Statement The authors have declared no competing interest.