Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum.

We studied how physiological properties of cerebellar climbing fiber (CF) to Purkinje cell (PC) synapses change during developmental transition from multiple to mono CF innervation onto each PC. From P3 to P6, differences in the strengths of multiple CFs became larger. Around P10, each PC was either monoinnervated by one strong CF (CF-mono) or multiply innervated by one strong CF (CF-multi-S) plus a few weaker CFs (CF-multi-W). We show that simultaneous release of multiple vesicles per site occurs normally from CF-multi-S, CF-mono, and mature CFs, but less frequently from CF-multi-W and neonatal CFs. We also present evidence suggesting that weaker CFs with lower probability of multivesicular release would be withdrawn preferentially. The results suggest that differentiation into strong and weak CFs with high and low probabilities of multivesicular release precedes developmental CF synapse elimination.