Abstract

Purkinje cells (PCs) in the cerebellar cortex can be divided into at least two main subpopulations: one subpopulation that prominently expresses ZebrinII (Z+), and shows a relatively low simple spike firing rate, and another that hardly expresses ZebrinII (Z–) and shows higher baseline firing rates. Likewise, the complex spike responses of PCs, which are evoked by climbing fiber inputs and thus reflect the activity of the inferior olive (IO), show the same dichotomy. However, it is not known whether the target neurons of PCs in the cerebellar nuclei (CN) maintain this bimodal distribution. Electrophysiological recordings in awake adult mice show that the rate of action potential firing of CN neurons that receive input from Z+ PCs was consistently lower than that of CN neurons innervated by Z– PCs. Similar in vivo recordings in juvenile and adolescent mice indicated that the firing frequency of CN neurons correlates to the ZebrinII identity of the PC afferents in adult, but not postnatal stages. Finally, the spontaneous action potential firing pattern of adult CN neurons recorded in vitro revealed no significant differences in intrinsic pacemaking activity between ZebrinII identities. Our findings indicate that all three main components of the olivocerebellar loop, i.e., PCs, IO neurons and CN neurons, operate at a higher rate in the Z– modules.

Highlights

  • The cerebellum integrates inputs from sensory, motor, cognitive and limbic systems in dedicated parts of its cortex and nuclei [1]

  • To confirm the dichotomous labelling of the cerebellar nuclei (CN) that was shown in the rat [21], we evaluated the presence of a clear separation between CN innervated densely by Z+ Purkinje cells (PCs) axons and by Z– PC axons assessing the eGFP labelling of ZebrinII in the CN in Slc1a6-EGFP mice [22,35,36]

  • The regularity of action potential (AP) firing was quantified by calculating the coefficient of variance (CV) and the CV2; we found that the regularity was not significantly different between neurons recorded in Z+ or Z– CN (CV: Z+: 1.25 ± 0.27; Z–: 1.02 ± 0.29; p = 0.6211, Mann–Whitney U test; CV2: Z+: 0.48 ± 0.02; Z–: 0.48 ± 0.03; p = 0.9957, Mann-Whitney U test; Figure 1D1,D2 respectively; Supplementary Table S1)

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Summary

Introduction

The cerebellum integrates inputs from sensory, motor, cognitive and limbic systems in dedicated parts of its cortex and nuclei [1]. Based on the connectivity of the pre-cerebellar afferent systems, i.e., mossy fibers and climbing fibers, as well as the cellular composition, the cerebellar cortex and cerebellar nuclei (CN) can be divided in modules. CN neurons are characterized by pacemaking activity, i.e., fire APs even in absence of any synaptic inputs [4] and receive excitatory mossy fiber and climbing fiber input via axon collaterals. The precise impact of the excitatory and inhibitory afferents has been studied in detail in silico, in vitro and in vivo [6,14,15,16,17,18], but without attention for the impact of the modular organization of the cerebellum

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