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Exp Brain Res. 2017 Sep;235(9):2787-2796. doi: 10.1007/s00221-017-5014-4. Epub 2017 Jun 20.

Aberrant connections between climbing fibres and Purkinje cells induce alterations in the timing of an instrumental response in the rat.

Author information

1
Laboratorio de Neurofisiología Experimental, Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, Camino de la Arboleda 300, Ex hacienda de San José de la Huerta, C.P. 58341, Morelia, Michoacán, Mexico.
2
Laboratorio de Neuroplasticidad de los Procesos Cognitivos, Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, Camino de la Arboleda 300, Ex hacienda de San José de la Huerta, C.P. 58341, Morelia, Michoacán, Mexico.
3
Instituto de Neurociencias Universidad de Guadalajara, Francisco de Quevedo 850, Col. Arcos Vallarta, C.P. 44130, Guadalajara, Jalisco, Mexico.
4
Laboratorio de Neurofisiología Experimental, Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, Camino de la Arboleda 300, Ex hacienda de San José de la Huerta, C.P. 58341, Morelia, Michoacán, Mexico. maesolco@yahoo.com.

Abstract

Cerebellar participation in timing and sensory-motor sequences has been supported by several experimental and clinical studies. A relevant role of the cerebellum in timing of conditioned responses in the range of milliseconds has been demonstrated, but less is known regarding the role of the cerebellum in supra-second timing of operant responses. A dissociated role of the cerebellum and striatum in timing in the millisecond and second range had been reported, respectively. The climbing fibre-Purkinje cell synapse is crucial in timing models; thus, the aberrant connection between these cellular elements is a suitable model for evaluating the contribution of the cerebellum in timing in the supra-second range. The aberrant connection between climbing fibres and Purkinje cells was induced by administration of the antagonist of NMDA receptors MK-801 to Sprague-Dawley rats at postnatal days 7-14. The timing of an operant response with two fixed intervals (5 and 8 s) and egocentric sequential learning was evaluated in 60-day-old adult rats. The aberrant connections caused a reduced accuracy in the timing of the instrumental response that was more evident in the 8-s interval and a reduced number of successive correct responses (responses emitted in the correct second without any other response between them) in the 8-s interval. In addition, an inability to incorporate new information in a sequence previously learned in egocentric-based sequence learning was apparent in rats with aberrant CF-PC synapses. These results support a relevant role for the cerebellum in the fine-tuning of the timing of operant responses in the supra-second range.

KEYWORDS:

Cerebellum; Climbing fibres; Purkinje cell; Timing; VGlut2

PMID:
28634887
DOI:
10.1007/s00221-017-5014-4
[Indexed for MEDLINE]

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