Shank3 gene mutation may impair brain’s ability to distinguish self from other

Researchers studying a mutation in a gene linked to autism spectrum disorders (ASD) say the mutation appears to disrupt the brain’s ability to distinguish “self” from “other.”

Daniel Lee and colleagues disrupted and then restored the expression of the Shank3 gene—which is mutated in about one percent of people with ASD—in adult male mice. They recorded the activity of neurons in the medial prefrontal cortex (a brain region linked to social behavior and cognition) when the mice were exposed to several scenarios with other mice.

The researchers say they found that “Shank3 disruption led to a reduction of neurons encoding the experience of other mice and an increase in neurons encoding the animal’s own experience.” The shift was associated with a loss of neurons’ ability to distinguish others from self.

The researchers were able to restore the function of the Shank3 gene in the experimental mice using the drug tamoxifen. They report, “Restoration of Shank3 expression in medial prefrontal cortex reversed this encoding imbalance and increased sociability over 5 to 8 weeks.” Selectively activating Shank3 in the medial prefrontal cortex rather than the entire brain resulted in the same changes.

The researchers conclude, “These findings reveal a neuronal-encoding process that is necessary for social behavior and that may be disrupted in ASD.”

—

“Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time,” Daniel K. Lee, S. William Li, Firas Bounni, Gabriel Friedman, Mohsen Jamali, Leah Strahs, Omer Zeliger, Pauline Gabrieli, Michael A. Stankovich, Jack Demaree, and Ziv M. Williams, Nature Neuroscience, July 12, 2021 (online). Address: Ziv Williams, Massachusetts General Hospital, Thier Research Building, 70 Blossom St, Boston, MA 02114, zwilliams@mgh.harvard.edu.

—and—

“Autism-linked mutation may blur brain’s boundary between self, others,” Angie Voyles Askham, Spectrum News, July 15, 2021.

This article originally appeared in Autism Research Review International, Vol. 35, No. 3, 2021