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

Elife. 2017 Oct 13;6:e29215. doi: 10.7554/eLife.29215.

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.

Keywords: Golgi cell; cerebellum; mouse; neuroscience; spillover.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials
  • Animals
  • Cerebellum / physiology*
  • Glutamic Acid / metabolism
  • Mice, Inbred C57BL
  • Nerve Net / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Receptors, Ionotropic Glutamate / metabolism
  • Receptors, Metabotropic Glutamate / metabolism

Substances

  • Receptors, Ionotropic Glutamate
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid