open access

https://hdl.handle.net/2115/47272

Development of an anatomical technique for visualizing the mode of climbing fiber innervation in Purkinje cells and its application to mutant mice lacking GluRδ2 and Cav2.1

英語

type 2 vesicular glutamate transporter

2011-03

Springer Japan

Anatomical Science International

86(1)

10-18

In the adult cerebellum, a single climbing fiber (CF) innervates proximal dendrites of Purkinje cells (PCs). This mono-innervation is established by developmental elimination of surplus CFs through homosynaptic competition among multiply-innervating CFs and heterosynaptic competition between CFs and parallel fibers, i.e., granule cell axons innervating distal PC dendrites. Although developmental process of CF mono-innervation and its defects in mutant and experimental animal models have been extensively studied by electrophysiological techniques, relevant morphological information had been poorly understood, because of the lack of neuroanatomical methods to distinguish CFs of different neuronal origins. Soon after the identification of type 2 vesicular glutamate transporter (VGluT2) that selectively detects CF terminals in the molecular layer, we developed a novel method of combined anterograde tracer labeling and VGluT2 immunohistochemistry. This method enables us to identify the mode (mono-innervation vs. multiple innervation) of CF innervation and the site of multiple innervation. Since then, we have applied this method to various kinds of gene-manipulated mice manifesting ataxia and other cerebellar phenotypes. In this review, we summarize experimental procedures for the combined tracer/VGluT2 labeling method, and then introduce what we learned with this method when applied to studies on the role of GluRδ2 and Cav2.1 in CF mono-innervation. This method has provided informative anatomical correlates to electrophysiological data and vice versa, and will extend our knowledge on the molecular and cellular mechanisms for development, plasticity, degeneration, and repair of the CF-PC projection system.

学術雑誌論文

Accepted Manuscript

The original publication is available at www.springerlink.com

1447-6959

1447-073X