Alterations in auditory midbrain processing is observed in both female and male mouse model of Fragile X Syndrome

Abstract

Auditory hypersensitivity is a common phenotype in Fragile X Syndrome. Electrophysiology studies at the inferior colliculus of male FMR1-knockout (KO) mice previously demonstrated increased neuronal firing, suggesting that the inferior colliculus is involved in auditory hypersensitivity. Here, we further explored whether the central nucleus of the inferior colliculus (ICc) is involved in auditory hypersensitivity in both female and male KO mice. Tone-evoked in-vivo electrophysiology recordings from ICc neurons of anesthetized (ketamine/xylazine) KO mice at both postnatal day 20 (P20) and 30 (P30) demonstrated increased spikes compared to age- and sex matched wild-type (WT) mice. Within the KO group, increased spikes were observed in females compared with male mice. Both female and male KO mice also displayed decreased minimum threshold and enhanced response duration at both ages. Additionally, female P30 KO mice displayed weaker inverse relationship between response latency and spike number compared to their WT counterparts. Regarding developmental changes, spike number decreased with maturation in both female and male KO mice. Response duration reduced with age in both sexes of both genotypes, while minimum threshold decreased in the male mice. Finally, we observed an age-related strengthening of the inverse relationship between response latency and magnitude only in the WT mice. Our findings indicate that the ICc display auditory processing deficits particularly in the female KO mice and in young animals highlighting the importance of including female subjects in future studies, and studying early development, which could be an ideal stage for interventions.