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The Journal of Neuroscience, February 27, 2008, 28(9):2179-2189; doi:10.1523/JNEUROSCI.4668-07.2008

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Behavioral/Systems/Cognitive
Selective Impairment of the Cerebellar C1 Module Involved in Rat Hind Limb Control Reduces Step-Dependent Modulation of Cutaneous Reflexes

Angelique Pijpers, ^* Beerend H. J. Winkelman, ^* Robert Bronsing, and Tom J. H. Ruigrok

Department of Neuroscience, Erasmus MC Rotterdam, 3000 CA Rotterdam, The Netherlands

Correspondence should be addressed to Tom J. H. Ruigrok, Department of Neuroscience, Erasmus MC Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Email: t.ruigrok{at}erasmusmc.nl

The cerebellum is divided into multiple parasagittally organized modules, which are thought to represent functional entities. How individual modules participate in cerebellar control of complex movements such as locomotion remains largely unknown. To a large extent, this is caused by the inability to study the contribution of individual modules during locomotion. Because of the architecture of modules, based on narrow, elongated cortical strips that may be discontinuous in the rostrocaudal direction, lesion of a complete module, without affecting neighboring modules, has not been possible. Here, we report on a new method for inducing a selective dysfunction of spatially separated parts of a single module using a small cortical injection of a retrogradely transported neurotoxin, cholera toxin b-subunit-saporin. We show that such a local injection into the C1 module results in climbing fiber and partial mossy fiber deafferentation of functionally related areas of this module, thereby resulting in a severe impairment of the whole module without affecting neighboring modules. A subsequent functional analysis indicates that such an impairment of the hindlimb part of the C1 module did not have a significant impact on skilled walking or overall stepping pattern. However, the modulation of cutaneously induced reflexes during stepping was severely diminished. We propose that the C1 module is specifically involved in the adaptive control of reflexes.

Key words: cerebellum; inferior olive; climbing fiber; Purkinje cell; degeneration; locomotion; reflex

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Received Oct. 15, 2007; revised Jan. 11, 2008; accepted Jan. 14, 2008.

Correspondence should be addressed to Tom J. H. Ruigrok, Department of Neuroscience, Erasmus MC Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Email: t.ruigrok{at}erasmusmc.nl

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