A novel window into autism through genetic targeting of striatal subdivisions

  • Awarded: 2014
  • Award Type: Research
  • Award #: 306140

A major goal of autism research is to understand the relationships among genetic etiology, altered developmental trajectory, aberrant neural circuits and behavioral symptoms characteristic of this disorder. Understanding how the functional activity of neural circuits is altered with cell-type resolution is likely to lead to more effective and targeted therapies. Among the neural circuits implicated in autism are ones involving the striatum, a structure buried deep within the brain that contributes to the evaluation and selection of behavior. Additionally, one gene associated with autism is SHANK3, which is important for the connections between neurons, including those within the striatum.

Ann Graybiel of the Massachusetts Institute of Technology and Josh Huang of Cold Spring Harbor Laboratory in New York are collaborating to test the hypothesis that changes in striatal circuits contribute to behaviors associated with autism. This circuitry may contribute to connecting emotional and evaluative signals with the selection of behaviors. Dysfunction of this interface may lead to some of the emotional, social and motor symptoms associated with autism, including anxiety, social withdrawal and indifference, and restricted, repetitive behaviors.

Graybiel, Huang and their colleagues aim to test this hypothesis using novel genetic tools. These tools allow for the manipulation of striatal neurons in both normal mice and SHANK3 mutant mice manifesting autism-like behaviors. The team plans to use these methods to evaluate the anatomical changes in this circuitry in the autism mice and to manipulate and record the activity of striatal cells during repetitive and social behaviors. Their goal is to use the manipulations to alleviate autism-like behaviors and evaluate the circuit’s potential as a target for therapies.

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