A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2020 | Number 2, Volume 34

Sensory hypersensitivity in individuals with ASD may stem from defects in inhibitory neurons

Many individuals with autism spectrum disorders (ASD) are hypersensitive to touch, sounds, and other sensory input, and a new study has identified one cause of this overreactivity. 

Qian Chen and colleagues studied mice lacking a gene called Shank3. Mutations of the Shank3 gene are linked to autism, and mice who are missing the Shank3 protein exhibit many behaviors—such as repetitive behaviors and avoidance of social interaction—that are associated with ASD. 

The researchers wanted to determine whether mice lacking the Shank3 gene also are hypersensitive to touch. To do this, they developed a way to measure the mice’s sensitivity to slight deflections of their whiskers. They then trained the mice, as well as a control group of normal mice, to exhibit behaviors that signaled when they felt their whiskers being touched. 

The researchers found that the mice missing the Shank3 gene noticed very slight deflections that the other mice missed. Guoping Feng, one of the study’s senior authors, says, “They are very sensitive to weak sensory input, which barely can be detected by wildtype [control] mice. That is a direct indication that they have sensory over-reactivity.” 

Next, the researchers studied activity in the brains of the mice using an imaging technique that measures calcium levels, which indicate neural activity, in specific cell types. They found that when the whiskers of the mice were touched, excitatory neurons in a brain area called the somatosensory cortex were overactive in the mice missing the Shank3 gene. 

Because synaptic activity should drop when Shank3 is missing, the researchers suspected that the hypersensitivity of the mice in the test group stemmed from low levels of Shank3 in inhibitory neurons that would normally reduce the activity of excitatory neurons. When they genetically engineered mice so they could turn off Shank3 expression only in inhibitory neurons in the somatosensory cortex, they indeed found that excitatory neurons in the mice were overactive even though these neurons had normal levels of Shank3. 

Feng comments, “If you only delete Shank3 in the inhibitory neurons in the somatosensory cortex, and the rest of the brain and the body is normal, you see a similar phenomenon where you have hyperactive excitatory neurons and increased sensory sensitivity in these mice.” 

He adds, “Our study is one of several that provide a direct and causative link between inhibitory defects and sensory abnormality, in this model [Shank3] at least. It provides further evidence to support inhibitory neuron defects as one of the key mechanisms in models of autism spectrum disorders.” He says the study suggests that reestablishing normal levels of neuronal activity could help reduce hypersensitivity in individuals with ASD.


Citations

“Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD,” Qian Chen, Christopher A. Deister, Xian Gao, Baolin Guo, Taylor Lynn-Jones, Naiyan Chen, Michael F. Wells, Runpeng Liu, Michael J. Goard, Jordane Dimidschstein, Shijing Feng, Yiwu Shi, Weiping Liao, Zhonghua Lu, Gord Fishell, Christopher I. Moore, and Guoping Feng, Nature Neuroscience, March 2, 2020 (online). Address: Guoping Feng, McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, [email protected]

—and— 

“New study may explain why people with autism are often highly sensitive to light and noise,” news release, Massachusetts Institute of Technology, March 2, 2020