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

Autor:	Heiney SA; Psychology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104., Wohl MP; Psychology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104., Chettih SN; Psychology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104., Ruffolo LI; Psychology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104., Medina JF; Psychology Department, University of Pennsylvania, Philadelphia, Pennsylvania 19104 jmed@psych.upenn.edu.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2014 Nov 05; Vol. 34 (45), pp. 14845-53.
DOI:	10.1523/JNEUROSCI.2820-14.2014
Abstrakt:	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. (Copyright © 2014 the authors 0270-6474/14/3414845-09$15.00/0.)
Databáze:	MEDLINE
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