Spike timing-dependent selective strengthening of single climbing fibre inputs to Purkinje cells during cerebellar development

Shaping functional neural circuits in developing brain involves activity-dependent refinement of early-formed redundant synapses. In the developing cerebellum, a one-to-one connection between a climbing fibre (CF) and a Purkinje cell (PC) is established by selective strengthening of a single CF followed by elimination of surplus CFs. Here we investigate developmental changes in CF-mediated responses in PCs by using in vivo whole-cell recordings and two-photon Ca2+ imaging. We show that each neonatal PC receives temporally clustered inputs from multiple CFs and temporal integration of these inputs is required to induce burst spiking and Ca2+ rise in PCs. Importantly, a single CF input closest to PC’s spike output is selectively strengthened during postnatal development. This spike timing-dependent selective strengthening is much less prominent in PC-selective P/Q-type voltage-dependent Ca2+ channel knockout mice. Thus, spike timing- and Ca2+-dependent plasticity appears to underlie the selection of a single ‘winner’ CF and the establishment of mature CF–PC connections. Cerebellar development involves activity-dependent strengthening of synaptic contacts between climbing fibres and Purkinje cells. Kawamura et al.show that temporally clustered multiple climbing fibre inputs contribute to characteristic burst spiking in immature Purkinje cells before specific contacts are strengthened.