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

The National Institute on Deafness and Other Communication Disorders awarded Northeast Ohio Medical University (Neomed) $440,000 on July 20, 2026, under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) to develop genetically modified Mongolian gerbil strains for auditory neuroscience research.

The project will create new gerbil lines with targeted fluorophore or recombinase expression in specific neuron types of the lateral superior olive, a brainstem region critical for sound localization. These strains will enable selective monitoring and manipulation of glycinergic inhibitory and glutamatergic excitatory neurons ex vivo and in vivo to advance understanding of cellular diversity in auditory processing circuits. The research employs recently developed viral vector-based CRISPR-Cas9 methods for embryo modification in the oviduct, a technique that, once established in gerbils, will accelerate production of additional genetically modified strains. Gerbils serve as a superior model to mice and rats for human hearing because they detect lower frequencies relevant to human speech and exhibit sound-localization mechanisms more analogous to human auditory function.

Work is performed in Rootstown, Ohio, with performance running through June 30, 2028. The award is classified as a Project Grant, the primary assistance type under NIDCD's research portfolio, funding salaries, equipment, supplies, and allowable direct and indirect costs of the research.

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.