Auditory cortical plasticity in a mouse model of Rett syndrome

  • Awarded: 2012
  • Award Type: Explorer
  • Award #: 261238

One of the most common symptoms shared among the autism spectrum disorders (ASD) is difficulty with social interaction. Frequently, this difficulty extends to problems perceiving and producing spoken language. The neural mechanisms for perceiving speech are not well understood, so how the genetic and developmental causes of ASD give rise to this symptom is not known. Stephen Shea and his colleagues at Cold Spring Harbor Laboratory in New York are using a mouse model of ASD to help close this gap in our understanding.

Rett syndrome is an ASD that usually occurs in girls and typically includes language impairments. Shea and his team found that mice carrying a gene mutation that causes Rett syndrome also exhibit difficulty in appropriately responding to the vocalizations of other mice. Specifically, mutant female mice were found to perform poorly on a maternal behavior test in which they must respond to the distress cries of mouse pups. The researchers’ findings suggest that this deficit is related to improper function and connectivity in a part of the brain, called the auditory cortex, which processes sound. Based on recordings from the auditory cortex, Shea and his colleagues suspect that the behavioral effects are linked to the strength and plasticity of synapses that release the inhibitory neurotransmitter GABA.

In another set of experiments, the researchers demonstrated that genetically restoring normal levels of GABA in the brain markedly improves maternal behavior in mutant mice. Their data further suggest that this rescue works by removing a brake on brain plasticity. Taken together, these studies are expected to reveal synaptic mechanisms that contribute to language and social behavior problems in ASD. Moreover, the behavioral rescue strategy may point the way toward potential therapeutic targets for Rett syndrome.

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