Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity

Angela K. Nietz, Jada H. Vaden, Luke T. Coddington, Linda Overstreet-Wadiche, Jacques I. Wadiche

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Golgi cells are the principal inhibitory neurons at the input stage of the cerebellum, providing feedforward and feedback inhibition through mossy fiber and parallel fiber synapses. In vivo studies have shown that Golgi cell activity is regulated by climbing fiber stimulation, yet there is little functional or anatomical evidence for synapses between climbing fibers and Golgi cells. Here, we show that glutamate released from climbing fibers activates ionotropic and metabotropic receptors on Golgi cells through spillover-mediated transmission. The interplay of excitatory and inhibitory conductances provides flexible control over Golgi cell spiking, allowing either excitation or a biphasic sequence of excitation and inhibition following single climbing fiber stimulation. Together with prior studies of spillover transmission to molecular layer interneurons, these results reveal that climbing fibers exert control over inhibition at both the input and output layers of the cerebellar cortex.

Original languageEnglish (US)
Article numbere29215
JournaleLife
Volume6
DOIs
StatePublished - Oct 13 2017
Externally publishedYes

Bibliographical note

Funding Information:
We thank members of the Wadiche labs for helpful comments throughout this project and Mary See-lig for technical assistance. This work was supported by NIH F31NS093960 (AKN), NIH NS064025 (LOW) and NIH NS065920 (JIW).

Publisher Copyright:
© Nietz et al.

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