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Functional Consequences of Fragile X Syndrome on Myelination in the Auditory Brainstem

Award Number: R01DC021733
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/15/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Functional Consequences of Fragile X Syndrome on Myelination in the Auditory Brainstem - PROJECT SUMMARY Myelination is a key component of neural transmission allowing for fast transfer of synaptic information. Disruption of myelination has been implicated in many disorders, including Fragile X Syndrome (FXS), the most common monogenic form of autism spectrum disorder (ASD). The auditory system, and specifically the auditory brainstem calyx of Held synapse, is one of the most highly myelinated synapses in the brain due to the temporal needs of auditory processing in encoding sound location information. Interestingly, auditory symptoms are also the most common sensory difficulties described by people with FXS, and many of these symptoms are related to dysfunction at the level of the auditory brainstem. It is possible that, like in other brain areas, auditory issues arise from disruption to the temporal capabilities, though changes in myelination, of the auditory brainstem sound localization circuit. Building on previous work, the research in this proposal will address whether myelination deficits underly auditory brainstem dysfunction. One prediction is that oligodendrocytes, the cells responsible for myelinating, are changed in their number or function in FXS (Aim 1). We will perform cell fate labeling and anatomical assays of oligodendrocyte myelination ability to test this prediction. Based on previous results, we predict functional changes to speed of transmission of neural information at the calyx of Held synapse (Aim 2). We will use in vitro conduction velocity and modeling studies to measure speed of transmission at the calyx synapse. Auditory intervention, which has promise in increasing myelination when introduced early in development, could be an effective therapy for FXS (Aim 3). We will expose animals at different stages of development to an auditory enrichment paradigm and measure impact of treatment on behavioral, physiological, and anatomical phenotypes in FXS and control mice. These three aims will provide important insight towards understanding how myelination changes relate directly to auditory brainstem function and whether intervention of this pathway is a potential therapeutic target in FXS using novel approaches. This research validates auditory- specific biomarkers and provides a non-invasive potential therapy to rescue auditory issues in FXS that may be relevant to broader ASD phenotypes due to similar underlying auditory symptomology. Importantly this research involves animal models of a human condition. We will also engage with community stakeholders (physicians, patient advocates, families, and people with autism) through a one-day interactive conference preceded by trainings that will help increase inclusion and accessibility to science for people in the disability community (Aim 4). This proposal will provide unparalleled opportunities for trainees and the broader scientific community to participate in cutting-edge scientific research and trainings regarding inclusivity while engaging and centering them in the ASD community.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $644,604 )
2026	2026	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Research Related to Deafness and Communication Disorders	001	1	3/18/2026	NEW	-$644,604
2026	2026	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Research Related to Deafness and Communication Disorders	002	1	3/20/2026	NEW	$644,604
2026	2026	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Research Related to Deafness and Communication Disorders	000	1	3/13/2026	NEW	$644,604
														Subtotal = $644,604

Grand Total All Awards = $644,604

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Functional Consequences of Fragile X Syndrome on Myelination in the Auditory Brainstem

Award Number: R01DC021733

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/15/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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