title: Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice.
abstract: Three decades of electrophysiological research on cerebellar cortical activity underlying Pavlovian conditioning have expanded our understanding of motor learning in the brain. Purkinje cell simple spike suppression is considered to be crucial in the expression of conditional blink responses (CRs). However, trial-by-trial quantification of this link in awake behaving animals is lacking, and current hypotheses regarding the underlying plasticity mechanisms have diverged from the classical parallel fiber one to the Purkinje cell synapse LTD hypothesis. Here, we establish that acquired simple spike suppression, acquired conditioned stimulus (CS)-related complex spike responses, and molecular layer interneuron (MLI) activity predict the expression of CRs on a trial-by-trial basis using awake behaving mice. Additionally, we show that two independent transgenic mouse mutants with impaired MLI function exhibit motor learning deficits. Our findings suggest multiple cerebellar cortical plasticity mechanisms underlying simple spike suppression, and they implicate the broader involvement of the olivocerebellar module within the interstimulus interval.
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Michiel M
authors.initials: MM
authors.lastname: ten Brinke
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Boele
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Jochen K
authors.initials: JK
authors.lastname: Spanke
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Potters
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands; Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK.
authors.forename: Katja
authors.initials: K
authors.lastname: Kornysheva
authors.affiliation: Physiologisches Institut, Christian-Albrechts-Universität, 24118 Kiel, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Wulff
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Anna C H G
authors.initials: AC
authors.lastname: IJpelaar
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands.
authors.forename: Sebastiaan K E
authors.initials: SK
authors.lastname: Koekkoek
authors.affiliation: Department of Neuroscience, Erasmus Medical Center, 3000 Rotterdam, the Netherlands; Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences (KNAW), 1105 Amsterdam, the Netherlands. Electronic address: c.dezeeuw@erasmusmc.nl.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001767:Blinking / Q000502:physiology; D002525:Cerebellar Cortex / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C091104:Purkinje cell protein L7