Properties of the nucleo-olivary pathway: an in vivo whole-cell patch clamp study

PLoS One. 2012;7(9):e46360. doi: 10.1371/journal.pone.0046360. Epub 2012 Sep 27.

Abstract

The inferior olivary nucleus (IO) forms the gateway to the cerebellar cortex and receives feedback information from the cerebellar nuclei (CN), thereby occupying a central position in the olivo-cerebellar loop. Here, we investigated the feedback input from the CN to the IO in vivo in mice using the whole-cell patch-clamp technique. This approach allows us to study how the CN-feedback input is integrated with the activity of olivary neurons, while the olivo-cerebellar system and its connections are intact. Our results show how IO neurons respond to CN stimulation sequentially with: i) a short depolarization (EPSP), ii) a hyperpolarization (IPSP) and iii) a rebound depolarization. The latter two phenomena can also be evoked without the EPSPs. The IPSP is sensitive to a GABA(A) receptor blocker. The IPSP suppresses suprathreshold and subthreshold activity and is generated mainly by activation of the GABA(A) receptors. The rebound depolarization re-initiates and temporarily phase locks the subthreshold oscillations. Lack of electrotonical coupling does not affect the IPSP of individual olivary neurons, nor the sensitivity of its GABA(A) receptors to blockers. The GABAergic feedback input from the CN does not only temporarily block the transmission of signals through the IO, it also isolates neurons from the network by shunting the junction current and re-initiates the temporal pattern after a fixed time point. These data suggest that the IO not only functions as a cerebellar controlled gating device, but also operates as a pattern generator for controlling motor timing and/or learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Cerebellar Nuclei / drug effects
  • Cerebellar Nuclei / physiology*
  • Feedback, Physiological / drug effects
  • GABA-A Receptor Antagonists / pharmacology
  • Learning / drug effects
  • Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microelectrodes
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Olivary Nucleus / drug effects
  • Olivary Nucleus / physiology*
  • Patch-Clamp Techniques
  • Receptors, GABA-A / physiology*
  • Stilbenes / pharmacology
  • Synaptic Transmission / drug effects

Substances

  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • Stilbenes
  • 4,4'-dinitro-2,2'-stilbenedisulfonic acid

Grant support

The present work has been funded by ZonMw Grant 917.96.347 (M.d.J). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.