title: Cerebellar control of gait and interlimb coordination.
abstract: Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more complex, multi-joint motor behaviors, such as locomotion performance and adaptation during obstacle crossing, is not well understood. Here, we investigated these functions using the Erasmus Ladder in cell-specific mouse mutant lines that suffer from impaired Purkinje cell output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Δγ2), and granule cell output (α6-Cacna1a). We found that locomotion performance was severely impaired with small steps and long step times in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Δγ2 and not significantly affected in α6-Cacna1a mice. Locomotion adaptation triggered by pairing obstacle appearances with preceding tones at fixed time intervals was impaired in all four mouse lines, in that they all showed inaccurate and inconsistent adaptive walking patterns. Furthermore, all mutants exhibited altered front-hind and left-right interlimb coordination during both performance and adaptation, and inconsistent walking stepping patterns while crossing obstacles. Instead, motivation and avoidance behavior were not compromised in any of the mutants during the Erasmus Ladder task. Our findings indicate that cell type-specific abnormalities in cerebellar microcircuitry can translate into pronounced impairments in locomotion performance and adaptation as well as interlimb coordination, highlighting the general role of the cerebellar cortex in spatiotemporal control of complex multi-joint movements.
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: Vinueza Veloz
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Kuikui
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Laurens W J
authors.initials: LW
authors.lastname: Bosman
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Potters
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Negrello
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Seepers
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Christos
authors.initials: C
authors.lastname: Strydis
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Sebastiaan K E
authors.initials: SK
authors.lastname: Koekkoek
authors.affiliation: Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. c.dezeeuw@erasmusmc.nl.|Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA, Amsterdam, The Netherlands. c.dezeeuw@erasmusmc.nl.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D005260:Female; D005684:Gait; D008124:Locomotion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009042:Motivation / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*
keywords: Erasmus Ladder; Granule cells; Interlimb coordination; Interneurons; Locomotion; Purkinje cells