Sensory hypersensitivity in mice with Grin2b mutations is associated with hyperactivity in the anterior cingulate cortex and increased connectivity in the brain. A research team led by Kim Eun-joon, Director of the Center for Brain Synaptic Dysfunctions, and Kim Seong-gi, Director of the Imaging Center for Neuroscience Research at the Institute of Basic Sciences (IBS), identified the underlying cause of sensory hypersensitivity in the autism spectrum. disorders (ASD).

Autism affects approximately 1 in 36 people and is characterized by significant difficulties in social interaction and communication. Approximately 90% of autistic patients also suffer from abnormal sensory hypersensitivity, which profoundly affects daily functioning. This hypersensitivity results in exaggerated or impaired responses to ordinary sensory stimuli such as sound, light, and touch, resulting in severe distress and subsequent social isolation. Not knowing exactly the brain region responsible for this sensory dysfunction hinders treatment attempts.

IBS researchers studied mouse model of autistic disorder with mutation in gene grin2b Encoding the GluN2B subunit of NMDA receptors. NMDA receptors, a type of glutamate receptor in the brain, have received attention in the context of autism due to their critical roles in synaptic transmission and neuronal plasticity. It was suggested that there was a gene mutation grin2b It turns out that it can cause ASD-like phenotypes, including sensory abnormalities, in mice and that certain brain mechanisms may play an important role.

Key findings and future research

The researchers monitored neural activity and functional connectivity in the brains of these mice using activity-related markers and functional magnetic resonance imaging (fMRI). The researchers found increased neuron activity in the anterior cingulate cortex (ACC) in these mice. The ACC is one of the higher-order cortical regions that has been extensively studied for cognitive and emotional brain functions, but understudied for sensory abnormalities associated with brain diseases.

Interestingly, when the hyperactivity of ACC neurons was inhibited using chemogenetic methods, sensory hypersensitivity was normalized; This suggests that ACC hyperactivity plays an important role in autism-related sensory hypersensitivity.

“This new study shows that the anterior cingulate cortex (ACC), known for its deep connection with cognitive and social functions, plays a role in sensory hypersensitivity in autism,” says director Kim Yunjun.

ACC hyperactivity was also associated with increased functional connectivity between the ACC and other brain regions. Both hyperactivity and hyperconnectivity of the ACC with various other brain regions are thought to be associated with sensory hypersensitivity in Grin2b mutant mice.

Director Kim Seong-hee says: “Previous studies suggested that peripheral neurons, or primary areas of the cerebral cortex, were important for ASD-related sensory hypersensitivity. These studies generally focused on the activity of only one region of the brain. In contrast, our study examined only the activity of the ACC.” “It also examines the hyperconnectivity between the ACC and different cortical/subcortical regions of the brain, giving us a more complete picture of the brain.”

The researchers plan to study the detailed mechanisms underlying increased excitatory synaptic activity and hyperconnectivity of neurons. They suspect that the absence of Grin2b expression may interfere with the normal process of weakening and shrinking of less active synapses, such that relatively more active synapses may participate in activity-dependent improvement of neural circuits. Other research interests include examining the role of ACC in other mouse models of ASD.