Tuesday, August 19, 2025 8/19/2025

Myelination Deficits Underlying Auditory Issues in Fragile X Syndrome

Award Number: R15HD105231
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/09/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2028

Group Awards By:

View Award Description

Myelination Deficits Underlying Auditory Issues in Fragile X Syndrome - Autism spectrum disorder (ASD) is characterized by an inability to function in environments with multiple competing sound sources, such as a noisy classroom. These auditory issues likely originate early in sound location processing that occurs in the brainstem. The projections that make up the auditory brainstem circuit that processes binaural (information from both ears) temporal, and intensity differences require heavily myelinated axons that convey precise information accurately from the cochlea to the brain. Our previous funded R15 showed decreased myelin thickness and axon fiber diameter in Fragile X Syndrome (FXS) mice, a monogenic form of ASD. We also showed a decrease in the latency of binaural waves in the auditory brainstem response (ABR), a non-invasive electrophysiological recording of this circuit, in FXS mice compared to controls. Lastly, animals have increased latencies to respond to reflexive auditory behavioral stimuli in FXS mice compared to controls. These data suggest that myelination deficits may underly binaural hearing difficulties in FXS, and perhaps ASD. We propose to further characterize myelination deficits in FXS using genetic approaches complemented with anatomical, physiological, and behavioral measures of myelination (microscopy, ABRs, and prepulse inhibition of the acoustic startle response). Primarily we are interested in understanding if myelination deficits we characterized in the original R15 are specifically due to loss of Fragile X messenger ribonucleoprotein (FMRP), the protein lacking in FXS, in neurons or in the myelinating glial cells (oligodendrocytes – OLs). We will use conditional knockout (cKO) or knockin (cKI) Fmr1 mice combined with Math5-cre, a cell type specific neuronal driver for auditory brainstem neurons, or MOBp a driver for OLs. We will then test animals on previously characterized auditory brainstem-specific tasks and approaches listed above to tease apart neuronal versus glial FMRP effects. Results from this study will determine how myelination contributes to binaural hearing processing issues in FXS and whether these deficits are specific to FMRP function in neurons or OLs. Lastly, we will use the same cKO and cKI animals and inject a viral vector with cre to express FMRP during specific time points to show when FMRP is acting in this circuit. All of the above experiments are approachable for undergraduate researchers thus funding from NIH increase student’s knowledge and ability to conduct basic research in line with the goals of the AREA program.


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: 2025 ( Subtotal = $444,238 )
2025	2025	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	002	2	8/1/2025	COMPETING CONTINUATION	$444,238
2025	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	001	1	7/4/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2021	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	000	1	7/4/2025	NEW	$0
														Subtotal = $444,238

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	002	1	8/22/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Trans-NIH Research Support	001	1	8/22/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2021	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	000	1	8/22/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $562,819 )
2022	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Trans-NIH Research Support	000	1	8/1/2022	SUPPLEMENT FOR EXPANSION	$437,653
2022	2022	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	001	1	8/8/2022	SUPPLEMENT FOR EXPANSION	$125,166
														Subtotal = $562,819

Issue Date FY: 2021 ( Subtotal = $442,099 )
2021	2021	OKLAHOMA STATE UNIVERSITY	401 WHITEHURST HALL	STILLWATER	OK	74078	PAYNE	USA	Child Health and Human Development Extramural Research	000	1	9/9/2021	NEW	$442,099
														Subtotal = $442,099

Grand Total All Awards = $1,449,156

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Myelination Deficits Underlying Auditory Issues in Fragile X Syndrome

Award Number: R15HD105231

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/09/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer