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Cerebellar-dependent expression of motor learning during eyeblink conditioning in head-fixed mice
Journal article   Open access   Peer reviewed

Cerebellar-dependent expression of motor learning during eyeblink conditioning in head-fixed mice

Shane A Heiney, Margot P Wohl, Selmaan N Chettih, Luis I Ruffolo and Javier F Medina
The Journal of neuroscience, Vol.34(45), pp.14845-14853
11/05/2014
DOI: 10.1523/jneurosci.2820-14.2014
PMCID: PMC4220020
PMID: 25378152
url
https://doi.org/10.1523/jneurosci.2820-14.2014View
Published (Version of record) Open Access

Abstract

Eyeblink conditioning in restrained rabbits has served as an excellent model of cerebellar-dependent motor learning for many decades. In mice, the role of the cerebellum in eyeblink conditioning is less clear and remains controversial, partly because learning appears to engage fear-related circuits and lesions of the cerebellum do not abolish the learned behavior completely. Furthermore, experiments in mice are performed using freely moving systems, which lack the stability necessary for mapping out the essential neural circuitry with electrophysiological approaches. We have developed a novel apparatus for eyeblink conditioning in head-fixed mice. Here, we show that the performance of mice in our apparatus is excellent and that the learned behavior displays two hallmark features of cerebellar-dependent eyeblink conditioning in rabbits: (1) gradual acquisition; and (2) adaptive timing of conditioned movements. Furthermore, we use a combination of pharmacological inactivation, electrical stimulation, single-unit recordings, and targeted microlesions to demonstrate that the learned behavior is completely dependent on the cerebellum and to pinpoint the exact location in the deep cerebellar nuclei that is necessary. Our results pave the way for using eyeblink conditioning in head-fixed mice as a platform for applying next-generation genetic tools to address molecular and circuit-level questions about cerebellar function in health and disease.
Animals Blinking Cerebellum - physiology Conditioning, Classical Male Mice Mice, Inbred C57BL Movement Restraint, Physical - instrumentation Restraint, Physical - methods

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