Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission.

Full Abstract

Classical conditioning of the eyeblink reflex is elicited by paired presentation of a conditioned stimulus and an unconditioned stimulus and represents a basic form of cerebellum-dependent motor learning. Purkinje cells and the deep nuclei receive convergent information of conditioned stimulus and unconditioned stimulus through the mossy fiber and climbing fiber projections, respectively. To explore the relative importance of these neural circuits and the underlying mechanism in associative eyeblink learning, we adopted a novel gene-manipulating technique, termed reversible neurotransmission blocking (RNB). In this technology, cerebellar granule cells specifically expressed neurotransmission-blocking tetanus toxin in a doxycycline (DOX)-dependent manner. Extracellular recording of Purkinje cells in awake RNB mice revealed that DOX treatment and withdrawal reversibly turned off and on simple spikes elicited by granule cell inputs, respectively, without interference with complex spikes evoked by climbing fiber inputs. Blockade of granule cell inputs to Purkinje cells abolished eyeblink conditioned responses (CRs) in a DOX-dependent manner. Importantly, when granule cell inputs recovered by removal of DOX, normal CRs were immediately produced in the DOX-treated, CR-negative RNB mice from the beginning of reconditioning. This learning process in RNB mice during DOX treatment was completely abolished by bilateral lesion of the interpositus nucleus before eyeblink conditioning. These results indicate that the convergent information at the interpositus nucleus is critical for acquisition and storage of learning in intimate association with the Purkinje cell circuit for expression of CRs in eyeblink conditioning.

Author information

Author/s: Wada, Norio (N); Kishimoto, Yasushi (Y); Watanabe, Dai (D); Kano, Masanobu (M); Hirano, Tomoo (T); Funabiki, Kazuo (K); Nakanishi, Shigetada (S);

Affiliation: Department of Systems Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2007-Oct; vol 104 (issue 42) : pp 16690-5

Dates: Created 2007/10/17; Completed 2007/12/13; Revised 2008/11/20;

PMID: 17923666, 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.

Comments and Corrections

ErratumIn: Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1097.

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