Rack1 Controls Parallel Fiber-Purkinje Cell Synaptogenesis and Synaptic Transmission.

Haihong Yang,Haitao Wu,Chen Zhang,Mengping Wei,Ying Li,Jiyan Zhang,Yan Wu,Fengjiao Liu,Qian Zhu,Chaojuan Yang,Juanxian Cheng

doi:10.3389/fncel.2019.00539

Abstract

Purkinje cells (PCs) in the cerebellum receive two excitatory afferents including granule cells-derived parallel fiber (PF) and the climbing fiber. Scaffolding protein Rack1 is highly expressed in the cerebellar PCs. Here, we found delayed formation of specific cerebellar vermis lobule and impaired motor coordination in PC-specific Rack1 conditional knockout mice. Our studies further revealed that Rack1 is essential for PF–PC synapse formation. In addition, Rack1 plays a critical role in regulating synaptic plasticity and long-term depression (LTD) induction of PF–PC synapses without changing the expression of postsynaptic proteins. Together, we have discovered Rack1 as the crucial molecule that controls PF–PC synaptogenesis and synaptic plasticity. Our studies provide a novel molecular insight into the mechanisms underlying the neural development and neuroplasticity in the cerebellum.

Highlights

The multiple functions of the brain depend on the precise communication between distinct types of neurons
Our studies demonstrated that receptor for activated C kinase 1 (Rack1) in Purkinje cells (PCs) is responsible for parallel fiber (PF)–PC synaptogenesis and synaptic transmission
Rack1 mutant mice appeared normal at postnatal day 21 (P21), as shown by similar body weight and cerebellar surface fissure compared to wild-type littermates (Figure 1E)

Summary

Introduction

The multiple functions of the brain depend on the precise communication between distinct types of neurons. Owing to the unique patterned foliation, typical “three-layer” cortex, and relatively simple cell types, the cerebellum serves as an ideal model for studying the development and function of synapses and brain circuits (Middleton and Strick, 1998). As the only efferent neurons in the cerebellar cortex, Purkinje cells (PCs) receive two types of excitatory synaptic inputs: climbing fibers and parallel fibers (PFs), and integrate cortical information for the deep cerebellar nuclei (Brown et al, 2012; Duguid et al, 2015; Nietz et al, 2017). PF–PC synapses are the fundamental connections in the cerebellar cortex, which play an essential role in cerebellar synaptic plasticity and motor coordination (Guan et al, 2014).

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Conclusion