Microcircuit endophenotypes for autism

  • Awarded: 2014
  • Award Type: Research
  • Award #: 339018

We are beginning to identify many genetic alterations, environmental factors and developmental processes that contribute to autism, but we do not yet understand how various molecular perturbations add up to cause the disorder. Vikaas Sohal and his colleagues at the University of California, San Francisco aim to identify possible alterations in the function of circuits in the prefrontal cortex that could contribute to autism.

One component of this project will build on previous work from Sohal’s laboratory, which found that the properties of a specific subpopulation of prefrontal neurons are altered in similar ways across multiple mouse models of autism. Now, the researchers plan to examine whether these neurons also exhibit abnormal activity during social behavior in mouse models of autism. This may help to more directly link the abnormal properties of these neurons to social deficits, and help researchers understand whether these abnormal properties represent potentially pathogenic or compensatory changes.

In previous work, Sohal and his group also found that the activity of prefrontal microcircuits in response to activation of acetylcholine receptors is abnormal in autism. They aim to explore possible underlying mechanisms involving abnormal modulation of inhibitory interneurons or neuronal connections by acetylcholine. Acetylcholine is a chemical that is released in the brain, and many researchers believe it sends signals related to attention. In this way, results from these studies might help researchers understand the basis for attentional deficits in autism.

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