The Genetics of Variation of the Wave 1 Amplitude of the Mouse Auditory Brainstem Response

Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3

“…There were no significant associations related to the changes in Wave I amplitude in response to eight or 32 kHz tone burst stimulation. At 16 kHz there was a single expression quantitative trait locus containing the Robo1 gene as previously reported (Boussaty et al, 2020). At 24 kHz, we identified a single locus on chromosome three was near the Nlgn1 gene (Figure S1A).…”

“…Genome-wide association study analysis of hybrid mouse diversity panel identifies a significant SNP in the Nlgn1 loci A functional screen aimed to identify genetic loci associated with deviations in suprathreshold Wave I in hybrid mouse diversity panel (HMDP) strains were previously reported and identified a region on chromosome 3 as a locus of interest (Boussaty et al, 2020;Lusis et al, 2016). This experiment considered 102 different mouse strains and performed a total of 635 ABR recordings to elucidate changes in cochlear output among the HMDP mice.…”

“…GWAS for ABR Wave I amplitude in the HMDP ( Bennett et al., 2010 ), were performed, as described previously ( Boussaty et al., 2020 ). Briefly, five-week-old female mice (n = 635) from 102 HMDP strains (n = 6-7 strains/strain) underwent ABR analysis, and peak to peak (P1-N1) values for Wave I amplitudes with 80 dB SPL stimuli at 8, 16, 24 and 32 kHz were measured and utilized for the GWAS study.…”

“…Moreover, Nrxn transcripts have been detected in transcriptomic studies of purified hair cells ( Cai et al., 2015 ; Scheffer et al., 2015 ). Independently, in a pioneering large-scale mouse GWAS study, a region on chromosome 3, where the Nlgn1 gene resides, was identified as a top candidate locus for reduced suprathreshold Wave I amplitude before and after noise trauma ( Boussaty et al., 2020 ).…”

Attenuation of Age-Related Hearing Impairment in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice Treated with Fatty Acid Synthase Inhibitor CMS121

“…Wave I occurs around 2 ms and represents the summated response from the spiral ganglion and auditory nerve (Akil et al 2016 ). Wave I suprathreshold amplitudes have been associated with significant differences in functional synaptic ribbon counts (Boussaty et al 2020 ). In this study, we did not observe any significant differences in suprathreshold wave I amplitudes between the CMS121-treated and untreated mice, although there were weak trends towards significance in the mid-range frequencies which may be further developed in future studies with larger samples of mice.…”