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

Full Abstract

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.

Author information

Author/s: Zbarska, S (S); Holland, E A (EA); Bloedel, J R (JR); Bracha, V (V);

Affiliation: Biomedical Sciences, 2032 Vet Med, Iowa State University, Ames, IA 50011, USA.

Grants: R01 NS21958 (Agency:NINDS NIH HHS) ; R01 NS36210 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Behavioural brain research (Behav Brain Res), published in Netherlands. (Language: eng)

Reference: 2007-Mar; vol 178 (issue 1) : pp 128-38

Dates: Created 2007/02/19; Completed 2007/05/04; Revised 2007/12/03;

PMID: 17222920, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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