caa a22 4500 606201769 CHVBK 20210128100950.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00429-014-0870-1 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0870-1 Cerebellar control of gait and interlimb coordination [Elektronische Daten] [María Vinueza Veloz, Kuikui Zhou, Laurens Bosman, Jan-Willem Potters, Mario Negrello, Robert Seepers, Christos Strydis, Sebastiaan Koekkoek, Chris De Zeeuw] 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. The Author(s), 2014 Purkinje cells nationallicence Interneurons nationallicence Granule cells nationallicence Locomotion nationallicence Interlimb coordination nationallicence Erasmus Ladder nationallicence Vinueza Veloz María Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Zhou Kuikui Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Bosman Laurens Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Potters Jan-Willem Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Negrello Mario Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Seepers Robert Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Strydis Christos Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Koekkoek Sebastiaan Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut De Zeeuw Chris Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3513-3536 1863-2653 220:6<3513 2015 220 429 https://doi.org/10.1007/s00429-014-0870-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0870-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Vinueza Veloz María Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Zhou Kuikui Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Bosman Laurens Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Potters Jan-Willem Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Negrello Mario Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Seepers Robert Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Strydis Christos Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Koekkoek Sebastiaan Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- De Zeeuw Chris Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3513-3536 1863-2653 220:6<3513 2015 220 429