In vivo analysis of synaptic activity in cerebellar nuclei neurons unravels the efficacy of excitatory inputs

Abstract

It is commonly agreed that the main function of the cerebellar system is to provide well-timed signals used for the execution of motor commands or prediction of sensory inputs. This function is manifested as a temporal sequence of spiking that should be expressed in the cerebellar nuclei projection neurons (CN). Whether spiking activity is generated by excitation or release from inhibition is still a hotly debated issue.

In an attempt to resolve this debate, we recorded intracellularly from CN neurons in anaesthetized mice and performed an analysis of synaptic activity that yielded a number of important observations. First, we demonstrate that CN neurons can be classified into four groups. Second, shape-index plots of the excitatory events suggest that they are distributed all over the dendritic tree. Third, the rise time of excitatory events is linearly related to the amplitude, suggesting that all excitatory events contribute equally to the generation of action potentials. Fourth, we identified a temporal pattern of spontaneous excitatory events that represent climbing fibre inputs and confirm the results by direct stimulation and analysis on harmaline evoked activity. Finally, we demonstrate that the probability of excitatory inputs to generate an AP is 0.1 yet half of the APs are generated by excitatory events. Moreover, the probability of a presumably spontaneous climbing fibre input to generate an AP is higher, reaching mean population value of 0.15. In view of these results, the mode of synaptic integration at the level of the CN should be re-considered.

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