Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors.

Gerrit Cornelis Beekhof,Joshua J White,Hannah Van Der Stok,Ingo Hms Nettersheim,Francesca Romana Fiocchi,Marit Runge,Scott Van Zoomeren,Martijn Schonewille,Freek E Hoebeek,Willem Ashwin Mak,Henk-Jan Boele,Catarina Osório,Bilian Xiong

doi:10.7554/elife.63668

Gerrit Cornelis Beekhof, Joshua J White + Show 11 more

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https://doi.org/10.7554/elife.63668

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Abstract

Distinct populations of Purkinje cells (PCs) with unique molecular and connectivity features are at the core of the modular organization of the cerebellum. Previously, we showed that firing activity of PCs differs between ZebrinII-positive and ZebrinII-negative cerebellar modules (Zhou et al., 2014; Wu et al., 2019). Here, we investigate the timing and extent of PC differentiation during development in mice. We found that several features of PCs, including activity levels, dendritic arborization, axonal shape and climbing fiber input, develop differentially between nodular and anterior PC populations. Although all PCs show a particularly rapid development in the second postnatal week, anterior PCs typically have a prolonged physiological and dendritic maturation. In line herewith, younger mice exhibit attenuated anterior-dependent eyeblink conditioning, but faster nodular-dependent compensatory eye movement adaptation. Our results indicate that specific cerebellar regions have unique developmental timelines which match with their related, specific forms of cerebellum-dependent behaviors.

Highlights

The parasagittal organization of the cerebellum is fundamental to confer specificity to the coordination and adaptation of behavior
Purkinje cells (PCs) were identified during the recording by the presence of SSs and complex spikes (CSs), while the consistent presence of a pause in SS following each CS (i.e., climbing fiber pause (CF pause)) confirmed that the recording was obtained from a single unit [40] (Figure1 A2-figure1 supplement1 A1)
While there is no difference in SS regularity in the young P12-P17 group (CV2, Z–: 0.51 ± 0.03, Z+: 0.51 ± 0.04, p= 0.94) there is a significant difference between Z– and Z+ PC regularity in the older groups

Summary

Introduction

The parasagittal organization of the cerebellum is fundamental to confer specificity to the coordination and adaptation of behavior This organization is based on cerebellar modules, i.e., anatomical and functional units [1,2,3], known to control specific tasks such as limb and finger movement [4, 5], compensatory eye movements [6,7,8,9] and associative motor learning [10,11,12,13,14]. PCs contribute to the proliferation of granule cells through the release of Sonic Hedgehog (Shh) [28], as well as the parasagittal organization of afferents [29] and interneurons [30] Concurrent to influencing this variety of developmental processes, PCs undergo their own migration, monolayer organization and growth of their large planar dendritic trees and axonal arbors. This study shows for the first time that PC subpopulations’ developmental timelines shape unique cerebellar circuitries that underlie different maturational profiles of specific cerebellar functions

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