Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus

Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation, but the patterns of activity required to fire postsynaptic CA3 pyramidal neurons remain poorly understood. We show that mossy fibers count the number of spikes to transmit information to CA3 pyramidal cells through a distinctive interplay between presynaptic calcium dynamics, buffering and vesicle replenishment. This identifies a previously unexplored information coding mechanism in the brain.