The role of glutamate receptor interacting proteins in autism

  • Awarded: 2011
  • Award Type: Research
  • Award #: 206683

Poor reciprocal social interaction is a devastating behavioral anomaly and a defining feature in people with autism spectrum disorders. Little is known about the cause and mechanisms of social deficits in autism, which hampers the development of effective therapies. Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system. It controls excitatory transmission by binding to a family of receptors, including AMPA receptors. Glutamate signaling defects causing an imbalance in excitatory and inhibitory neuronal circuits are implicated in autism; however, the molecular mechanisms remain unknown. The research teams of Richard Huganir and Tao Wang at Johns Hopkins University in Baltimore propose to study mutations in AMPA-receptor signaling genes that have been found in people with autism and to generate mouse models with these human mutations to investigate mechanisms of social deficits in autism.

Previous studies from the Huganir and Wang teams showed that mutations in glutamate receptor interacting protein 1 (GRIP1) contribute to increased severity in autism social deficits1. These autism-associated mutations were found to cause abnormal trafficking of AMPA receptors in neurons. The researchers then generated and conducted behavioral studies on mice that carry the same mutation. The mutant mice exhibited severe defects in social interactions, similar to individuals with autism who carry this mutation. Future plans include testing whether drugs that modulate AMPA receptor functions can improve social deficits in these mice. The researchers hope the results will provide valuable insights into the regulatory mechanisms of autism social behaviors and guide the development of novel AMPA-receptor-based therapies to correct social deficits in autism.



1.Mejias R. et al. Proc. Natl. Acad. Sci. USA 108, 4920-4925 (2011) PubMed
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