Inferior olivary inactivation abolishes conditioned eyeblinks: extinction or cerebellar malfunction?

Behav Brain Res. 2007 Mar 12;178(1):128-38. doi: 10.1016/j.bbr.2006.12.012. Epub 2006 Dec 17.


The inferior olive (IO) is a required component of neural circuits controlling the classical conditioning of eyeblink responses. Previous reports indicated that lesioning or inactivating the IO abolishes conditioned eyeblinks (CRs), but there was disagreement regarding the timing of the CR performance deficit. As a result, it was not clear whether IO inactivation produces unlearning of CRs or a non-specific dysfunction of cerebellar circuits. Since most of these studies used methods that could block unrelated axons passing through the IO region, additional experiments are required to further elucidate IO function, using inactivating agents that act selectively on cell bodies. In the present study, the IO was inactivated using the glutamate receptor antagonist DGG and the GABA-A receptor agonist muscimol in rabbits performing well-learned CRs. Effects of inactivating the IO on CR expression and on neuronal activity in the anterior cerebellar interposed nucleus (IN) were examined. We found that either blocking excitatory glutamate inputs or activating inhibitory GABA inputs to the IO abolished CRs. This effect occurred with variable delay following drug injections. Additional experiments, in which post-injection testing was delayed to allow for drug diffusion, revealed invariably immediate suppression of CRs. This demonstrated that suppressing IO activity using DGG or muscimol does not induce unlearning of CRs. Single-unit recording during DGG injections revealed that CR suppression was paralleled by a dramatic suppression of IN neuronal activity. We concluded that inactivating the rostral parts of the IO complex abolishes CRs by producing a tonic malfunction of cerebellar eyeblink conditioning circuits.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Analysis of Variance
  • Animals
  • Cerebellum / cytology
  • Cerebellum / physiology*
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology
  • Conditioning, Eyelid / drug effects
  • Conditioning, Eyelid / physiology*
  • Excitatory Amino Acid Agents / pharmacology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology*
  • GABA Agonists / pharmacology
  • Male
  • Muscimol / pharmacology
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology*
  • Neurons / physiology
  • Olivary Nucleus / physiology*
  • Rabbits
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / physiology


  • Excitatory Amino Acid Agents
  • GABA Agonists
  • Receptors, Glutamate
  • Muscimol