Cerebellar plasticity and learning in a mouse model of autism

  • Awarded: 2013
  • Award Type: Research
  • Award #: 311232

Autism is often described as the ‘intense world syndrome,’ referring to the observation that individuals with autism experience sensory input as too intense. This has led to the hypothesis that excitability is too high in the brains of those with autism, possibly as a result of impaired pruning of synapses during development.

Christian Hansel and his colleagues at the University of Chicago examined pruning at one of the few locations in the brain where it can be directly measured, using electrophysiological tools: the climbing fiber to Purkinje cell synapse, which plays a role in signaling ‘errors’ in the sensorimotor world and the initiation of motor adaptation and learning. They found that in mice with a duplication of chromosomal region 15q11-13 — one of the most frequent types of genetic aberration in autism — pruning at this synapse is impaired. This finding provides one of the most direct demonstrations that synaptic pruning is indeed affected in autism.

There is a second aspect of this work: About 80 percent of children with autism have motor problems. Hansel and his team found that the lack of climbing fiber elimination causes an abnormal strength of this synaptic input and saturation of the synaptic plasticity mechanism that mediates learning and long-term depression (LTD) at parallel fiber-Purkinje cell synapses. This deregulation of LTD is the likely reason for the impairment in motor learning seen in these mice. Together, their findings provide one plausible explanation for why motor function is altered in autism.

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