Anxiety-like behavior in deaf Ebf1 conditional knockout mice.

Abstract

INTRODUCTION: Hearing is critical for communication and clinical evidence suggests that hearing loss can lead to poorer mental well-being including social isolation, anxiety, depression, and cognitive decline. Deaf animal models offer opportunities to investigate the impact of hearing loss on behavioral correlates of mental health while controlling for genetic variability and shared etiological factors such as environmental stressors, aging, and metabolic diseases. We previously showed that conditional deletion of Ebf1 in the inner ear causes deafness. We hypothesize that otic-specific Ebf1 knockout (KO) mice recapitulate neurobehavioral alterations experienced in congenital deafness. METHODS: Slc26a9P2A-Cre and Ebf1 floxed mice were crossed previously to generate the otic-specific Ebf1 conditional KO. We measured auditory brainstem response and behavior in groups of otic-specific Ebf1 conditional KO mice and Cre-negative littermate controls (WT). We performed behavioral tests including elevated plus maze, acoustic startle, locomotor activity, forced swim, and Y-maze. RESULTS: We found that the KO mice spend significantly less time than WT mice in the open arms of the elevated plus maze. KO mice also show significantly increased latency to enter the open arms. Acoustic startle response was decreased in KO mice vs. WT controls and pre-pulse inhibition was also reduced in the KO, consistent with elevated hearing thresholds. We found no significant differences in exploratory behavior, forced swim immobility time, or other behavioral measures examined. CONCLUSIONS: Our findings demonstrate that deaf otic-specific KO mice are indeed a model for the study of effects of hearing loss on clinically relevant behavioral correlates. Our results provide new empirical evidence that hearing loss contributes to anxiety, which is consistent with clinical evidence that anxiety is associated with hearing loss in older adults.