Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism

Nat Commun. 2014 Nov 24;5:5586. doi: 10.1038/ncomms6586.

Abstract

A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning--a form of cerebellum-dependent motor learning--is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres--a model for activity-dependent synaptic pruning--is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / physiopathology*
  • Blinking / physiology*
  • Cerebellum / physiology
  • DNA Copy Number Variations / genetics*
  • Disease Models, Animal
  • Electrophysiology
  • Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Activity / genetics
  • Motor Activity / physiology*
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Patch-Clamp Techniques
  • Purkinje Cells / physiology
  • Synapses / physiology