New Study Identifies Brain Region Linked To Altered Social Interactions in Autism Model

New Study Identifies Brain Region Linked To Altered Social Interactions in Autism Model

A new study claims to show that in a mouse model, neuroscientists were able to reverse social traits associated with autism by restoring a specific region in the fore-brain.

Often it can be easy to identify the symptoms of a disorder, but it can be more difficult to isolate the underlying causes of the disorder itself. While some psychiatric disorders can be linked directly to particular genes, the actual brain regions and the mechanisms underlying it and not very well understood.

Autism Spectrum Disorder (ASD) has been associated with mutations or deletions of the SHANK3 gene, as well as a rare disorder known as Phelan-McDermid Syndrome. Mice that have the SHANK3 mutations also display some traits associated with autism, such as dislike of loud noises and fast movements and avoidance of social interactions, but the region in the brain that is responsible for this behavior has not been identified.

A new study by MIT and fellow colleagues in China may provide some clues to the neuroscience behind the causal circuits in the brain responsible for social deficits accompanying ASD.

From the Abstract:

“Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.”

Many regions in the brain have been implicated in social interactions, such as the prefrontal cortex (PFC) but the new study focuses instead on the anterior cingulate cortex, or the ACC. The ACC is a brain region noted for its role in social functions in humans and animal models. The ACC is also known to play a role in fundamental cognitive processes, including cost-benefit calculation, motivation, and decision making.

The study discovered that structural and functional disturbances at the synapses, or connections between excitatory neurons in the ACC. The study went on the further show that the loss of SHANK3 in excitatory ACC neurons alone was enough to disrupt communication between neurons and led to reduced activity of the neurons during behavioral tasks reflecting social interaction.

Having isolated the ACC neurons in social preference and interactions in SHANK3 mutated mice, the researchers then tested whether activating those same neurons could help alleviate these behaviors. Via Optogenetics and specific drugs, researchers claim they were able to activate the ACC neurons and found improved behaviors in the mutated mice.

The study was funded by the Natural Science Foundation of China, Mr. Feng was supported by a NIMH Grant, the Poitras Center for Psychiatric Disorders Research at the McGovern Institute at MIT, and the Hock E. Tan and K. Lisa Young Center for Autism Research at McGovern Institute at MIT.

Researchers will continue to explore the ACC neurons and hope it will provide insight into the Autism Spectrum Disorder.

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