Inferior olive hypertrophy and cerebellar learning are both needed to explain ocular oscillations in oculopalatal tremor

Simon Hong, R. John Leigh, David S. Zee, Lance M. Optican

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

A new model of cerebellar learning explains how the cerebellum can generate arbitrary output waveforms to adjust output timing in the classical delay conditioning. This model can also reproduce the low frequency ocular oscillations seen in oculopalatal tremor (OPT). A novel circuit in the cerebellum uses both interneurons (INs) and Purkinje cells (PC) to control timing. Brain lesions that cause OPT give rise to hypertrophy of the inferior olive (IO) and an increase in conductance through gap junctions among IO neurons. When our model is changed in this way, the heavily coupled IO becomes an oscillator and generates synchronous spike trains at 1-2 Hz. These synchronized spikes do not produce the large amplitude, aperiodic waveforms of OPT. However, the synchronized IO signal goes to the cerebellar cortex (flocculus) directly, on climbing fibres, and indirectly, on mossy fibres from the vestibular nuclei. This creates a pathological association between the IO pulse trains on mossy and climbing fibres in PC. Variable pendular ocular oscillations emerged from the cerebellum model after learning this association. Since electrotonic coupling of IO cells depends on connexin proteins, drugs that block gap junctions, such as anti-malarial agents, might provide a novel therapy for OPT.

Original languageEnglish (US)
Title of host publicationUsing Eye Movements as an Experimental Probe of Brain function A Symposium in Honor of Jean Buttner-Ennever
PublisherElsevier
Pages219-226
Number of pages8
ISBN (Print)9780444531636
DOIs
StatePublished - Jan 1 2008

Publication series

NameProgress in Brain Research
Volume171
ISSN (Print)0079-6123

Keywords

  • classical conditioning
  • gap junction
  • interaction
  • interneuron
  • mGluR
  • Purkinje cell
  • waveform

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hong, S., Leigh, R. J., Zee, D. S., & Optican, L. M. (2008). Inferior olive hypertrophy and cerebellar learning are both needed to explain ocular oscillations in oculopalatal tremor. In Using Eye Movements as an Experimental Probe of Brain function A Symposium in Honor of Jean Buttner-Ennever (pp. 219-226). (Progress in Brain Research; Vol. 171). Elsevier. https://doi.org/10.1016/S0079-6123(08)00631-6