By Richard A. Felix II, Ph.D.
Genetically modified “knockout” mice (red, right) show differences in the timing of auditory brainstem responses compared with wild-type (left, blue) mice.
As many as 10 percent of preschool children exhibit some form of developmental speech processing disorder that cannot be attributed to known causes, such as hearing loss or neurological problems.
Such listening disorders are accompanied by typical hearing, as determined by traditional hearing tests that assess inner ear function, indicating that these processing deficits are located within the brain. Studies of central auditory processing disorders (CAPD) have identified degraded timing of midbrain activity as a predictor of listening difficulties in adults and children, but the source of dysfunction is unresolved.
Genetically engineered knockout mouse models in which a specific gene is knocked out, or removed, can be used to discover how the processing of timing information may be altered in the developing auditory system and, as a result, how problems with temporal processing impacts listening in humans.
Our mouse model involves the disruption of cholinergic signaling. Nerve cells that are cholinergic use the neurotransmitter acetylcholine to send messages (in contrast to adrenergic nerve cells that use epinephrine or related substances to transmit signals). The CHRNA7 gene, which affects the function of acetylcholine, is considered to be a primary candidate gene causing a wide spectrum of neurodevelopmental disorders, including autism spectrum disorder. Genome-wide studies have found that CHRNA7 is one of a few genes associated with reading disability and specific language impairment, supporting the hypothesis that CHRNA7 is an important gene for the development of language.
In our study published in the Journal of Neurophysiology in July 2019, we examined the temporal processing of knockout mice whose cholinergic signaling is disrupted compared with wild-type mouse controls. We found degraded, abnormal timing of neural activity in the knockout mice at the level of the auditory brainstem and midbrain. These findings underscore the importance of cholinergic signaling in types of neurodevelopmental and auditory processing disorders.
Understanding the contribution of cholinergic signaling to auditory processing may increase our understanding of language impairment and may assist in the development or refinement of noninvasive diagnostic tests, pharmacological treatments, and behavioral therapeutic strategies.
Richard A. Felix II, Ph.D., is a postdoctoral researcher in the Hearing and Communications Lab at Washington State University Vancouver. His 2016 Emerging Research Grant was generously funded by the General Grand Chapter Royal Masons International.
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