Understanding the Underpinnings of Sensory Hypersensitivity in SCN2A-Associated Autism


Analysis Spotlight

Individuals who expertise sensory hypersensitivity have a heightened consciousness of and reactivity to sensory stimuli, akin to sound, sight, contact, and style. Sensory hypersensitivity is a symptom usually related to autism spectrum dysfunction (ASD), as greater than 90% of kids who’ve ASD expertise this sensory problem.

Researchers analyzing the neural underpinnings of sensory hypersensitivity have usually centered on the position of the forebrain—an space within the entrance of the mind concerned in processing sensory stimuli and regulating behaviors and feelings. Nonetheless, new analysis means that mind circuitry that helps sensory reflexes—which happen at a a lot earlier stage of sensory processing—is also contributing to this sensitivity.

What did the researchers do?

To be taught extra concerning the neural underpinnings of sensory hypersensitivity, a brand new NIMH-funded examine by Chenyu Wang, Ph.D., a researcher on the College of California, San Francisco, and colleagues checked out mind areas that management the vestibulo-ocular reflex. This reflex stabilizes pictures on our retina by inflicting our eyes to maneuver in the other way of our head.

A drawing of the eye-tracking helmet worn by child participants in the study. Credit: Wang et. al., 2024, Neuron.

Drawing of the helmet used within the examine. Credit score: Wang et. al., 2024, Neuron.

The researchers examined how the mind controls this reflex in individuals and mice with a genetic mutation known as SCN2A lack of perform. SCN2A lack of perform has the strongest affiliation with ASD of any identified genetic mutation. The SCN2A mutation impacts the best way neurons transfer charged particles, known as ions, into and out of the cell. This, in flip, impacts the best way cells (together with these concerned with the vestibulo-ocular reflex) electrically talk with one another.

Members included youngsters between the ages of three and 10 with the SCN2A lack of perform genetic mutation identified with ASD, in addition to similarly-aged youngsters who didn’t have the mutation or identified ASD. All contributors wore a light-weight helmet that tracked each their eye and head actions. The researchers discovered that the vestibulo-ocular reflex was hypersensitive in youngsters with the SCN2A lack of perform genetic mutation in comparison with these with out the mutation. The researchers discovered that mice with the Scn2a lack of perform mutation additionally confirmed this sample of heightened vestibulo-ocular reflex conduct.

A section of mouse cerebellum. Credit: Wang et. al., 2024, Neuron.

A bit of mouse cerebellum. Credit score: Wang et. al., 2024, Neuron.

To search out out what may be inflicting this sample of vestibulo-ocular reflex conduct, the researchers recorded electrical exercise within the brains of mice with the Scn2a lack of perform mutation. They discovered that the exercise between cells concerned in supporting the vestibulo-ocular reflex (known as Purkinje and cerebellar granule cells) didn’t change in response to differing ranges of head velocity and motion, not like what could be seen in mice with out this genetic mutation. This lack of cell exercise adaptation was discovered to be pushed by the Scn2a lack of perform mutation within the granule cells.

To see if a typical vestibulo-ocular reflex could possibly be restored, the researchers administered a gene-based therapeutic to mice that focused the Sn2a lack of perform mutation after they had been both 3 days outdated or 30 days outdated. The researchers had been in a position to totally restore typical vestibulo-ocular reflex conduct in mice handled at 3 days outdated, however restoration was solely partial in mice handled at 30 days outdated, suggesting there may be an early developmental interval that cements facets of this reflex.

What do the outcomes imply?

This examine shines mild on the neural processes concerned in a particular symptom related to ASD—sensitivity to sensory stimuli. As well as, for the reason that vestibulo-ocular reflex was hyperactive in youngsters with SCN2A lack of function-associated autism, the findings counsel an eye fixed reflex take a look at could possibly be used sooner or later as an early identifier of ASD. Moreover, a gene-based therapeutic restored typical vestibulo-ocular reflex conduct when given to very younger mice with Scn2a lack of perform, suggesting a attainable option to ameliorate sensorimotor dysfunction sooner or later. The examine additionally means that cerebellum-dependent reflexes, just like the vestibulo-ocular reflex, might show to be generalizable and translatable markers for figuring out the effectiveness of potential therapies that purpose to deal with sensorimotor signs generally skilled by individuals with ASD.

Reference

Wang, C., Derderian, Ok. D., Hamada, E., Zhou, X., Nelson, A. D., Kyoung, H., Ahituv, N., Bouvier, G., & Bender, Ok. J. (2024). Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD. Neuron. https://doi.org/10.1016/j.neuron.2024.01.029 

Grants

MH125536 , MH135209 , MH125978 

Leave a Reply

Your email address will not be published. Required fields are marked *

Contact Us

Give us a call at (385) 312-0787  or fill in the form below and we will contact you. We endeavor to answer all inquiries within 24 hours on business days.

Error: Contact form not found.