title: Behavioral correlates of complex spike synchrony in cerebellar microzones.
abstract: The olivo-cerebellar system is crucial for smooth and well timed execution of movements based on sensory and proprioceptive cues. The inferior olive (IO) plays a pivotal role in this process by synchronizing its activity across neurons internally through connexin36 gap junctions and providing a timing and/or learning signal to the cerebellum. Even though synchrony achieved through electrical coupling in IO cells is generally thought to be important in timing motor output, a direct relation between timing of movement and synchrony of olivary discharges has never been demonstrated within functional microcomplexes using transgenics. Here we combined in vivo, two-photon calcium imaging of complex spikes in microcomplexes of Purkinje cell (PC) dendrites with high-speed filming of tail, trunk, and limb movements in awake wild-type and connexin36-deficient mice. In wild types at rest, functional clusters of PCs were poorly defined with synchrony correlations that were relatively small and spatially limited to mediolateral distances of ∼50 μm, whereas during locomotion synchrony of the same PCs increased in strength and extended over distances spanning multiple microzones that could be correlated to specific components of sharp and well bounded movements. Instead, connexin36-deficient mice exhibited prolonged and desynchronized complex spike activity within PC microcomplexes both at rest and during behavior. Importantly, the mutants also showed concomitant abnormalities in the execution of spinocerebellar reflexes, which were significantly slower and more gradual than in wild-type littermates, particularly following sensory perturbations. Our results highlight the importance of modulation of synchronous activity within and between cerebellar microcomplexes in on-line temporal processing of motor output.
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands and.
authors.forename: Jornt R
authors.identifier: http://orcid.org/0000-0001-6647-2041
authors.initials: JR
authors.lastname: De Gruijl
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands and.
authors.forename: Tycho M
authors.identifier: http://orcid.org/0000-0002-7444-9279
authors.initials: TM
authors.lastname: Hoogland
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands and Department of Neuroscience, Erasmus MC, 3000 CA Rotterdam, The Netherlands c.dezeeuw@erasmusmc.nl.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000032:analysis; D020013:Calcium Signaling; D002531:Cerebellum / Q000503:physiopathology*; D017630:Connexins / Q000172:deficiency / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D058407:Electroencephalography Phase Synchronization / Q000502:physiology*; D005260:Female; D017629:Gap Junctions / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D009069:Movement Disorders / Q000235:genetics / Q000503:physiopathology*; D009847:Olivary Nucleus / Q000503:physiopathology*; D011689:Purkinje Cells / Q000502:physiology / Q000648:ultrastructure; D000097004:Gap Junction delta-2 Protein
chemical_list: D002118:Calcium; D017630:Connexins; D000097004:Gap Junction delta-2 Protein
keywords: complex spike; connexin36; in vivo; microzone; motor control; olivo-cerebellar system