Familiar objects can prevent autism-like behaviour in mouse model

The emergence of autism traits can result from different factors, such as a person’s environment and genetic background. FMI researchers and their Novartis collaborators showed that exposing mice with an autism mutation to a new environment can trigger autism-like behaviors — through faulty signaling in the brain. However, adding familiar objects to the environment can rescue these defects, suggesting that behavioral therapies involving familiar features may help to prevent the emergence of autism traits in predisposed people.

Every person on the autism spectrum is unique, and autistic traits may differ significantly even between siblings with similar genetic backgrounds. To investigate the factors that might contribute to the emergence of autism, researchers in the Caroni group and their colleagues at the FMI and the Novartis Institutes for BioMedical Research set out to study mice who carry a mutation in the SHANK3 gene.

SHANK3 encodes a protein that helps neurons communicate throughout the brain. Mutations in this gene have been associated with autism and intellectual disability, and deletions of the chromosomal region containing SHANK3 lead to Phelan-McDermid syndrome, a condition characterized by intellectual disability, problems with speech, and autism.

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“Nobody expected that experiencing a novel context would have such a major impact on engagement, and that this can be prevented by including familiar objects,” says study senior author Pico Caroni. The findings may have implications for autistic people. “It might be possible to expand the comfort zone of a person with autism by introducing familiar things in a new environment,” Caroni says.

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The researchers found that in SHANK3 mice, dopamine signals in the tail of striatum induced when mice explored objects were much larger than in control mice. Preventing dopamine signaling in this brain area rescued the engagement problems seen upon subsequent exposures. These findings suggest that a memory induced in the tail of striatum by elevated dopamine levels results in reduced engagement with objects or other mice. “Dopamine signaling at the first encounter may be part of the signaling machinery that leads to the long-term memory of not engaging in that context,” Caroni says.

Further experiments showed that in control mice, the activity of a group of neurons that project from the prelimbic cortex, a brain area involved in social engagement, to the tail of striatum mediates engagement with objects or other mice after the animals are exposed to a new environment. Activating these neurons in SHANK3 mice prevented the animals’ lack of engagement with their peers, the team found.


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