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mGluR5 in sound localization circuits

Award Number: R01DC022539
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: 02/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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mGluR5 in sound localization circuits - Project Summary Spontaneous neuronal activity plays a pivotal role in the development of brain circuits. The development of central auditory circuits depends on the temporally patterned spontaneous activity originating in the cochlea (a peripheral mechanism). Disruption of this activity results in abnormal development of auditory circuits and compromised auditory processing and behavior. Our pilot work revealed that activation of metabotropic glutamate receptor 5 (mGluR5), one member of group I mGluRs, triggered temporally patterned spontaneous activity in auditory brainstem neurons, implying a potential central mechanism underlying the spontaneous activity necessary for the development and maturation of auditory circuits. To fully understand the mechanism, we will examine in-depth the anatomy, physiology, and loss-of-function consequences of mGluR5 in the development of the brainstem sound localization (BSL) circuit in the mouse. Our central hypothesis is that mGluR5 is necessary for proper formation and function of the circuit, and dysfunctional mGluR5 leads to compromised circuit formation underlying binaural processing. Specifically, we seek to determine: 1) the spatiotemporal pattern of mGluR5 expression; 2) the physiological functions of mGluR5; and 3) which developmental aspects of the circuit are disrupted if mGluR5 is eliminated. We hypothesize that: 1) mGluR5 expression is developmentally regulated; 2) mGluR5 modulates neuronal properties in the circuit; and 3) elimination of mGluR5 disrupts development of the BSL circuit. To test these hypotheses, we will use advanced anatomical analyses, in vitro and in vivo physiology, optical imaging, immunohistochemistry, electron microscopy, in combination with genetic manipulations to pursue two specific aims. In Aim 1, we will investigate the anatomy and physiology of mGluR5 during development and into maturation. We will determine the cellular and subcellular localization of mGluR5, and then examine the modulatory functions and mechanisms of mGluR5 in regulating intrinsic excitability and producing patterned spontaneous activity in the circuit. In Aim 2, we will investigate the mechanisms underlying malformation and malfunction of the circuit in genetically manipulated mice. By using the powerful Cre-loxP system, we are able to eliminate mGluR5 exclusively on certain transmitter pathways. We predict that the elimination of mGluR5 compromises the core neuronal properties underlying the function of the circuit. Upon the successful completion of this project, we expect to obtain an in-depth understanding of mGluR5 neuromodulation in the development of the BSL circuit, providing a central mechanism underlying the patterned spontaneous activity critical for the development of auditory circuits. mGluR5 has been the target for drug development for treating numerous brain disorders. Our study will provide a foundation for pharmaceutical interventions that may prevent or rescue malformation and dysfunction of auditory circuits.


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 = $631,040 )
2026	2026	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 STATE ROUTE 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Research Related to Deafness and Communication Disorders	000	1	1/22/2026	NEW	$631,040
														Subtotal = $631,040

Grand Total All Awards = $631,040

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mGluR5 in sound localization circuits

Award Number: R01DC022539

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: 02/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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