Different numbers of conjunctive stimuli induce LTP or LTD in mouse cerebellar Purkinje cell

Abstract Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell (PC) synapses plays an important role in cerebellum-related motor coordination and learning. LTD is induced by the conjunction of PF stimulation and climbing fiber (CF) stimulation or somatic PC depolarization, while long-term potentiation (LTP) is induced by PF stimulation alone. Thus, it has been considered that different types of stimulation induce different types of synaptic plasticity. However, we found that a small number of conjunctive stimulations (PF + somatic depolarization) induced LTP, and not a small size of LTD. This LTP was not associated with changes in paired-pulse ratio and was dependent on nitric oxide, suggesting postsynaptic LTP. This LTP was also induced by a smaller number of physiological conjunctive stimulations, utilizing PF and CF stimulation. These results suggested that a larger number or longer period of conjunctive stimulation is required to induce LTD by overcoming LTP. Ca2+ imaging during physiological conjunctive stimulation at 0.5 Hz for 180 s (90 times), which was required for LTD induction, demonstrated that the peak amplitude of the Ca2+ signal at the PC dendritic region increased gradually, responding to the repetitive conjunctive stimulation. Instantaneous peak amplitude was not different between the early phase (50–60 s, 26th-30th) and late phase (170–180 s, 86th-90th), but the average amplitude for 60 s was larger in the later phase than in the early phase. These results show that LTD overcomes LTP, and increased Ca2+ integration or a number of stimulations is required for LTD induction.