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Genetically modified gerbils to advance investigation of cellular properties underlying timing- and intensity-based sound localization in mammals with a hearing frequency range more similar to humans

Award Number: R21DC024044
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: 07/20/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Genetically modified gerbils to advance investigation of cellular properties underlying timing- and intensity-based sound localization in mammals with a hearing frequency range more similar to humans - Project abstract Sound localization is critical for selective attention and speech comprehension in normal sound environments. These abilities are disrupted by hearing loss and in children with central auditory processing disorder (CAPD). Verbal communication takes place at lower frequencies which rats and particularly mice do not hear well. Additionally, sound localization mechanisms differ between high and low frequency hearing mammals. Mongolian gerbils (gerbils) hear lower frequencies and are a better model for human hearing, but genetically modified strains are lacking. The superior olivary complex (SOC) in the brainstem compares information between the two ears enabling sound localization. Principal neurons of the lateral superior olive (LSO PNs) are critical for these functions. There is cellular diversity in the LSO that is not well-understood that may inform how sounds are processed and how extracted information is organized in higher processing centers. This project will produce new gerbil strains that will allow us to selectively target glycinergic inhibitory and glutamatergic excitatory LSO PN types by means of fluorophore or recombinase expression. This will provide maximum future flexibility to not only target but monitor and manipulate activity of specific types of neurons ex vivo and in vivo. These gerbil strains will be created using recently developed methods for viral vector targeting of CRISPR-Cas9-based modification of very early phase embryos post copulation in the oviduct. Development of this method in gerbils will allow for the rapid production of additional genetically modified strains. Gerbils and other low-frequency-hearing mammals, but not mice and rats, have ipsilaterally projecting excitatory (IPE) LSO PNs. In gerbils these neurons are also biased to the low frequency limb of the LSO. Nothing is known of the cellular properties of IPE LSO PNs that may underlie their function in the circuit; however, preliminary studies show that gerbils have distinct LSO PNs that mice lack. We will reveal the intrinsic membrane properties and morphology of IPE LSO PNs by injecting retrograde tracer into the inferior colliculus (IC) unilaterally in cell-type-reporter gerbils. We can then target IPE LSO PNs for ex vivo whole-cell recordings and morphological reconstruction. Our hypothesis is that the IPE LSO pathway evolved with low-frequency hearing, and these neurons have cellular properties specialized for time- coding functions. Having a distinct projection pattern from other LSO PNs would allow for the differential utilization of this information in the IC. Our proposal is innovative in our treatment of LSO PNs as a diverse network with cellular properties tuned for multiple functional roles. It is technically innovative in our implementation of knock-in gerbil strains. We are also using an innovative method to produce these gerbil lines that will benefit the wider scientific community. This project will advance the use of a more appropriate model organism for the study of human hearing and yield foundational insights into the cellular organization of the SOC which may be disrupted by hearing loss and contribute to poorly understood disease states such as CAPD.


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 = $440,000 )
2026	2026	NORTHEAST OHIO MEDICAL UNIVERSITY	4209 STATE ROUTE 44	ROOTSTOWN	OH	44272	PORTAGE	USA	Research Related to Deafness and Communication Disorders	000	1	7/21/2026	NEW	$440,000
														Subtotal = $440,000

Grand Total All Awards = $440,000

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Genetically modified gerbils to advance investigation of cellular properties underlying timing- and intensity-based sound localization in mammals with a hearing frequency range more similar to humans

Award Number: R21DC024044

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: 07/20/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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