Although psychiatric disorders can be associated with certain genes, the brain regions and mechanisms that underlie certain disorders are not well understood. Mutations or deletions of the SHANK3 gene are strongly linked to autism spectrum disorder (ASD) and a related rare disorder, Phelan-McDermid syndrome. Also, mice with SHANK3 mutations exhibit some of the features associated with autism, including the avoidance of social interactions, but the brain regions responsible for this behavior have not been identified.
A recent study by neuroscientists at MIT and colleagues in China provides clues to the neural circuits that underlie social deficiencies associated with ASD. The work published in Nature Neuroscience found that structural and functional impairments of the anterior cingulate cortex (ACC) of SHANK3 mutant mice are associated with altered social interactions.
"Neurobiological mechanisms of social deficits are very large" Guoping Feng, James W. and Patricia T. Poitras, professor at MIT and one of the leading authors of the study. "These results complement the mapping of the neural circuits responsible for this social deficit in ASD models to another piece of the puzzle."
The work Nature Neuroscience is the result of a collaboration between Feng, who is also an investigator at the McGovern Institute of MIT and senior scientist at the Stanley Center for Psychiatric Research of the Broad Institute, as well as Wenting Wang and Shengxi Wu of the However, China's social interactions, including the prefrontal cortex (PFC) and its projections on brain regions, including the nucleus accumbens and the habenula, could not be clearly correlated with altered social interactions in SHANK3 knockout mice in Xi'an fourth medical university Be associated.
The authors instead focused on the ACC, a brain region known for its role in social functions in human and animal models. It is also known that the ACC plays a role in basic cognitive processes, including cost-benefit analysis, motivation and decision-making.
In mice without SHANK3, the researchers found structural and functional disorders at the synapses or connections between arousal neurons in the ACC. The researchers further demonstrated that the loss of SHANK3 in excitatory ACC neurons alone was sufficient to disrupt the communication between these neurons, resulting in unusually reduced activity of these neurons during behavioral tasks that reflected social interaction.
In SHANK3 knockout mice, the authors then tested whether activation of the same neurons can rescue this behavior. Using optogenetics and specific drugs, the researchers activated the ACC neurons and detected improved social behavior in the SHANK3 mutant mice autism, "explains Wenting Wang, co-author of the study." This will help us understand the neural mechanisms of social behavior as well to better understand social deficits in neurodevelopmental disorders. "
Previous clinical studies showed that anatomical structures in the ACC in people with ASD altered and / or disturbed initial evidence that the results of SHANK3 mice could also apply to these individuals ,
Autism gene in association with brain and behavioral deficits in mice
Baolin Guo et al. Dysfunction of the anterior cingulate cortex underlies social deficits in mutant Shank3 mice, Nature Neuroscience (201
McGovern Institute of Brain Research
Brain region associated with altered social interactions in the autism model (2019, July 27)
retrieved on July 27, 2019
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