Synaptic transmission and plasticity at inputs to murine cerebellar Purkinje cells are largely dispensable for standard nonmotor tasks

J Neurosci. 2013 Jul 31;33(31):12599-618. doi: 10.1523/JNEUROSCI.1642-13.2013.

Abstract

In addition to its well established role in motor coordination, the cerebellum has been hypothesized to be involved in the control of cognitive and emotional functions. Although a cerebellar contribution to nonmotor functions has been supported by recent studies in human and monkey, it remains to be clarified with an in-depth, systematic approach in mouse mutants. Here we subjected four different cerebellar cell-specific mouse lines whereby the excitatory or inhibitory input to Purkinje cells (PCs) and/or PC postsynaptic plasticity were compromised, to a wide battery of standard cognitive and emotional tests. The four lines, which have all been shown to suffer from impaired motor learning without being ataxic, were tested for social behavior using a sociability task, for spatial navigation using the Morris watermaze, for fear responses using contextual and cued conditioning, and general anxiety using the open-field task. None of the four cerebellum-specific genetic perturbations showed significantly impaired cognitive or emotional behavior. In fact, even without correction for multiple comparisons, only 5 of 154 statistical comparisons showed a marginally significant deficit. Therefore, our data indicate that none of the perturbations of cerebellar functioning studied here affected the cognitive or emotional tests we used. This suggests that there may be a differential impact of the murine and human cerebellum on nonmotor functions. We hypothesize that these differences could be a consequence of the remarkable enlargement of the cerebellar hemispheres during the latest phase of vertebrate phylogeny, which occurred in parallel with the evolution of the cerebral cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affective Symptoms / genetics
  • Affective Symptoms / physiopathology
  • Animals
  • Calcium Channels, N-Type / deficiency
  • Calcium Channels, N-Type / metabolism
  • Cerebellum / cytology*
  • Cognition Disorders / genetics
  • Cognition Disorders / physiopathology
  • Conditioning, Psychological / physiology
  • Exploratory Behavior / physiology
  • Fear / psychology
  • Female
  • Functional Laterality
  • Gene Expression Regulation / genetics
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Psychomotor Performance / physiology
  • Purkinje Cells / cytology*
  • Purkinje Cells / physiology*
  • Rotarod Performance Test
  • Smell / genetics
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*

Substances

  • Calcium Channels, N-Type
  • voltage-dependent calcium channel (P-Q type)