A research team at the Institute for Basic Science has identified the primary cause of sensory hypersensitivity related to autism spectrum disorders (ASD). ASD affects 1 in 36 individuals and is characterized by social and communication challenges, with around 90% of patients experiencing abnormal sensory hypersensitivity. This hypersensitivity leads to exaggerated or dampened responses to stimuli and can cause significant stress and social withdrawal. However, the specific brain region responsible for this dysfunction was previously unknown, making treatment difficult.
The researchers studied an ASD mouse model with a mutation in the Grin2b gene, which encodes the GluN2B subunit of NMDA receptors in the brain. NMDA receptors play a crucial role in synaptic transmission and neural plasticity, making them relevant to autism research. It was hypothesized that the Grin2b gene mutation would induce ASD-like symptoms, including sensory abnormalities, and that certain brain mechanisms would be involved. Using activity-dependent markers and functional magnetic resonance imaging (fMRI), the scientists monitored neural activity and connectivity in the mice’s brains.
They found increased neuronal activity in the anterior cingulate cortex (ACC) of the mice, a brain region associated with cognitive and emotional functions but understudied in relation to sensory abnormalities. When the hyperactivity in the ACC was inhibited using chemogenetic methods, the sensory hypersensitivity in the mice was normalized, highlighting the crucial role of ACC hyperactivity in autism-related sensory issues. The heightened functional connectivity between the ACC and other brain regions was also linked to sensory hypersensitivity in the Grin2b mutant mice.
The researchers believe that both the hyperactivity and hyperconnectivity of the ACC with other brain regions are involved in sensory hypersensitivity in these mice. This study challenges previous research that focused on peripheral neurons or primary cortical areas as being important for ASD-related sensory hypersensitivity. By investigating not only the activity of the ACC but also its connections with other brain regions, the researchers provide a more comprehensive understanding of the brain’s involvement in sensory processing in autism.
Moving forward, the team plans to delve into the detailed mechanisms underlying the increased excitatory synaptic activity and neuronal hyperconnectivity observed in the mice. They suspect that the lack of Grin2b expression may disrupt the normal synaptic weakening and pruning processes, leading to altered neural circuits in an activity-dependent manner. Additionally, they aim to explore the role of the ACC in other mouse models of ASD to broaden their understanding of sensory hypersensitivity in autism. This study was published in the journal Molecular Psychiatry and sheds light on the neurological underpinnings of sensory issues in individuals with ASD.