Understanding what causes the superior hearing abilities of people with WBS will not only help advance research on their ability to distinguish sounds, but may provide targets for treating the disease. provide insight into the mechanisms underlying the auditory abilities of humans. For example, some people with WBS have perfect pitch. This is the ability to distinguish notes or frequencies without a reference guide.

“WBS stands out among neurodevelopmental disorders because of its high prevalence of superior musical and verbal abilities compared to children in the general population, despite severe learning disabilities,” said the lead author. Stanislav Zakharenko, M.D., said. St. Jude Department of Developmental Neurobiology. “We were fascinated by it and wanted to learn more about how the impairment caused by the loss of 27 genes could help individuals acquire greater-than-normal abilities in auditory processing. .

Excitation of neurons in the auditory cortex

The mouse model of WBS has an enhanced ability to discriminate sound frequencies. These mice also have improved frequency coding in the auditory cortex, the part of the brain that processes sound. The researchers showed that the enhanced ability to discriminate between frequencies is caused by hyperexcitable interneurons in the auditory cortex.

To understand the cell biology underlying the improved hearing ability of WBS patients, researchers performed RNAseq experiments. This data led researchers to her neuropeptide receptor, called VIPR1, that is decreased in the auditory cortex of WBS patients. A reduction in VIPR1 was also seen in brain organoids, an advanced model created in the laboratory using human induced pluripotent stem cells.

Scientists found that the transcription factor Gtf2ird1, encoded by one of 27 genes lost in WBS patients, regulates VIPR1. Deletion or overexpression of VIPR1 in the auditory cortex can mimic or reverse the auditory effects seen in WBS. therefore, Gtf2ird1 Downregulates VIPR1 responsible for the effects of WBS on hearing.

“We didn’t know much about VIPR1 until it appeared in the data because the role of this receptor family in the brain is underestimated compared to other neuromodulatory or neurotransmitter receptors,” said the first author. Christopher Davenport, St. Jude Division of Developmental Neurobiology. “Our findings indicate that they can have profound effects on information processing and behavior, and are likely related to other behaviors and diseases.”

“This study suggests that reducing neuronal hyperexcitability may be a general mechanism for treating WBS by targeting VIPR1,” said Zakharenko. says. “It also opens up new directions for learning about musicality and how the brain distinguishes between sounds, based on these findings in the WBS model.”

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Materials provided St. Jude Children’s Research Hospital. Note: Content may be edited for style and length.