Key brain region implicated in sensory problems in autism

Summary: Researchers have identified the anterior cingulate cortex (ACC) as a crucial area linked to sensory hypersensitivity in autism spectrum disorder (ASD). This sensory hypersensitivity, which affects around 90% of autistic people, causes abnormal responses to stimuli like sound and light, complicating daily activities and social interactions.

The study used a mouse model with a Grin2b gene mutation known to mimic autism-like traits, including sensory abnormalities. By inhibiting ACC hyperactivity, researchers were able to normalize these hypersensitivities, suggesting new avenues for potential treatments.

Highlights:

1. Main results: Increased neuronal activity in the anterior cingulate cortex (ACC) of mice with a Grin2b mutation is linked to the sensory hypersensitivity observed in ASD.
2. Mode of intervention: Researchers successfully normalized sensory hypersensitivity by chemogenetically inhibiting ACC hyperactivity, thereby indicating its central role in the disorder.
3. Future research directions: The study opens new avenues for exploring how increased excitatory synaptic activity and neuronal hyperconnectivity in the ACC contribute to sensory problems in ASD, with potential implications for the development of targeted therapies.

Source: Institute of Basic Sciences

A research team led by Director KIM Eunjoon of the Center for Brain Synaptic Dysfunctions and Director KIM Seong-Gi of the Neuroimaging Research Center of the Institute of Basic Sciences (IBS) has identified the main cause of hypersensitivity sensory linked to autism spectrum disorders. (TSA).

Autism affects approximately 1 in 36 people and is marked by significant challenges with social interaction and communication. Approximately 90% of autistic patients also suffer from abnormal sensory hypersensitivity that profoundly affects their daily functioning.

This hypersensitivity results in exaggerated or blunted responses to common sensory stimuli such as sound, light, and touch, leading to considerable stress and increased social withdrawal.

The precise brain region responsible for this sensory dysfunction is unknown, hampering treatment efforts.

IBS researchers studied an ASD mouse model with a mutation in the smile2b gene, which encodes 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 crucial role in synaptic transmission and neuronal plasticity.

It was hypothesized that the smile2b a genetic mutation in mice would induce ASD-like phenotypes, including sensory abnormalities, and that certain brain mechanisms could play an important role.

The researchers monitored neuronal activity and functional connectivity in the brains of these mice using activity-dependent markers and functional magnetic resonance imaging (fMRI). In these mice, researchers found increased neuronal activity in the anterior cingulate cortex (ACC).

The ACC is one of the higher order cortical regions that has been widely studied for cognitive and emotional brain functions but has been understudied for sensory abnormalities related to brain diseases.

Interestingly, when hyperactivity of ACC neurons was inhibited using chemogenetic methods, sensory hypersensitivity was normalized, indicating the central role of ACC hyperactivity in autism-associated sensory hypersensitivity.

Director KIM Eunjoon says: “This new research demonstrates the involvement of the anterior cingulate cortex (ACC), known for its profound association with cognitive and social functions, in the sensory hypersensitivity of autism. »

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

Director KIM Seong-Gi says, “Previous studies attributed the importance of peripheral neurons or primary cortical areas to ASD-related sensory hypersensitivity.

“These studies often focused only on the activity of a single brain region. In contrast, our study investigates not only ACC activity, but also brain-wide hyperconnectivity between the ACC and various 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 neuronal hyperconnectivity.

They suspect that the lack of Grin2b expression might inhibit the normal process of weakening and pruning of less active synapses, so that relatively more active synapses can participate in the refinement of neuronal circuits in a manner dependent on activity.

Other areas of research interest are investigating the role of ACC in other mouse models of ASD.

About this research news on autism and sensory processing

Author: William Suh
Source: Institute of Basic Sciences
Contact: William Suh – Institute for Basic Sciences
Picture: Image is credited to Neuroscience News

Original research: Free access.
“Functional hyperconnectivity linked to the anterior cingulate cortex mediates sensory hypersensitivity in Grin2b mutant mice” by KIM Eunjoo et al. Molecular Psychiatry

Abstract

Functional hyperconnectivity linked to the anterior cingulate cortex causes sensory hypersensitivity in Grin2b mutant mice

Sensory abnormalities are observed in approximately 90% of people with autism spectrum disorder (ASD), but the underlying mechanisms are poorly understood.

GluN2B, a subunit of the NMDA receptor that regulates long-term depression and circuitry refinement during brain development, has been strongly implicated in ASD, but if GRIN2B the mutations leading to sensory abnormalities remain unclear.

We report here that smile2b-mutant mice exhibit behavioral sensory hypersensitivity and brain hyperconnectivity associated with the anterior cingulate cortex (ACC). smile2b-mutant mice with a patient-derived C456Y mutation (smile2b^C456Y/+) exhibit sensory hypersensitivity to mechanical, thermal and electrical stimuli via supraspinal mechanisms. c-fos and functional magnetic resonance imaging indicate that the ACC is hyperactive and hyperconnected with other brain regions under baseline and stimulation conditions.

ACC pyramidal neurons exhibit increased excitatory synaptic transmission. Chemogenetic inhibition of ACC pyramidal neurons normalizes ACC hyperconnectivity and sensory hypersensitivity.

These results suggest that GluN2B critically regulates cortical connectivity and sensory brain functions related to ASD.