Evolving Models of Pavlovian Conditioning: Cerebellar Cortical Dynamics in Awake Behaving Mice

Michiel M ten Brinke, Henk-Jan Boele, Jochen K Spanke, Jan-Willem Potters, Katja Kornysheva, Peer Wulff, Anna C H G IJpelaar, Sebastiaan K E Koekkoek, Chris I De Zeeuw

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1977-88
Number of pages12
JournalCell Reports
Volume13
Issue number9
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

Bibliographical note

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

  • Animals
  • Behavior, Animal/physiology
  • Blinking/physiology
  • Cerebellar Cortex/metabolism
  • Electrophysiological Phenomena
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins/genetics
  • Purkinje Cells/metabolism

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