Brain region related to modified social interactions in the autism model

Although psychiatric disorders may be related to particular genes, brain regions and underlying mechanisms of particular disorders are not well understood. Mutations or deletions of the SHANK3 gene are strongly badociated with Autism Spectrum Disorder (ASD) and a related rare disorder called Phelan-McDermid Syndrome. Mice with SHANK3 mutations also exhibit some traits badociated with autism, including avoidance of social interactions, but brain regions responsible for this behavior have not been identified.

A new study by MIT neuroscientists and Chinese colleagues provides clues to the neural circuits underlying social deficits badociated with ASD. The paper, published in Nature Neuroscience, found that structural and functional alterations of the anterior cingulate cortex (ACC) of mutant SHANK3 mice are related to altered social interactions.

"The neurobiological mechanisms of social deficits are very complex and involve many brain regions, even in a mouse model," says Guoping Feng, professor James W. and Patricia T. Poitras at MIT and one of the lead authors of the study. "These findings add another piece of the puzzle to mapping the neural circuits responsible for this social deficit in ASD models."

the Nature Neuroscience The paper is the result of a collaboration between Feng, also a researcher at the McGovern Institute at MIT and a senior scientist at the Broad Institute's Center for Psychiatric Research, and Wenting Wang and Shengxi Wu at the Fourth University of Medicine. Xi's military. China.

A number of brain regions have been implicated in social interactions, including the prefrontal cortex (PFC) and its projections on brain regions, including the nucleus accumbens and habenula, but these studies have not allowed definitively link PFC to modified social interactions observed in SHANK3 inhibition mice. .

In the new study, the authors instead focused on ACC, a brain region recognized for its role in social functions in humans and animal models. ACC is also known to play a role in fundamental cognitive processes, including cost-benefit calculation, motivation, and decision-making.

In mice lacking SHANK3, the researchers found structural and functional perturbations at the level of synapses, or connections, between the excitatory neurons of ACC. The researchers then showed that the loss of SHANK3 in ACC-excitatory neurons was enough to disrupt communication between these neurons and lead to an abnormally reduced activity of these neurons in behavioral tasks reflecting social interaction.

After having involved these ACC neurons in the preferences and social interactions in SHANK3 knockout mice, the authors then checked if the activation of these same neurons could rescue these behaviors. Using optogenetics and specific drugs, the researchers activated the ACC neurons and discovered improved social behavior in SHANK3 mutant mice.

"We then plan to explore the brain regions located downstream of ACC, which modulate social behavior in normal mice and autism models," says Wenting Wang, co-correspondent author of l & # 39; study. "This will help us better understand the neural mechanisms of social behavior, as well as social deficits in neurodevelopmental disorders."

Previous clinical studies have shown that ACC anatomical structures are altered and / or dysfunctional in people with ASD, an initial indication that results obtained with SHANK3 mice may also be true in these individuals.

Provided by
McGovern Institute for Brain Research