The overall objective of the proposed experiments is to aid in developing a reliable animal model for age-related hearing loss (ARHL) using behavioral methodologies. ARHL, or presbycusis, has four distinct types and is the most common disorder among older humans. This condition is sexually dimorphic, with males losing hearing earlier than females, especially in the high frequency range. It is critical to establish a reliable anatomical, physiological, and behavioral animal model for ARHL in order to understand the basis of presbycusis, and for developing future diagnostic and treatment strategies. Mice are frequently used to study and model ARHL due to similarities in human and mouse cochleae and in genetic make up. Mice also emit ultrasonic vocalizations (USVs) that may be used for communication purposes, similar to speech in humans. Previous research that utilized electrophysiological methodologies established that the CBA/CaJ mouse strain is an appropriate model for late-onset hearing loss. These mice exhibit ARHL sex differences in auditory brainstem responses (ABRs) for pure tones between 12 and 15 months of age, with males showing higher ABR thresholds than females. However, ABR audiograms are less sensitive and have been shown to over- and underestimate auditory deficits. A majority of the previous research on AHRL used electrophysiological measures of hearing in mice, leading to a severe underrepresentation of behavioral experiments in the aging literature. In humans, hearing loss for pure tones and speech is assessed using behavioral measures. If mice are going to continue to be used as ARHL models for humans, we need to establish hearing loss using similar methodologies. Kobrina and Dent (2016) used operant conditioning procedures with positive reinforcement to show that CBA/CaJ mice exhibit ARHL, however much later in life than established by ABR studies in the same strain of mouse. Thus ABR studies may miss a significant portion of mouse?s lifespan and hearing abilities. In fact, this strain is capable of detecting 42 kHz pure tone and USVs up to 34 month of age. The behaviorally measured ARHL sex differences were present for detecting USVs, but not for 42 kHz tones, conflicting with previous ABR findings. For CBA/CaJ mice to continue to be used as a model for ARHL, it is critical that we understand how female and male mice lose hearing for simple and complex auditory signals using behavioral methods in awake animals. The goal of current research is to use operant conditioning procedures to establish a pure tone aging audiogram, to examine the effects of stimulus duration on detection across lifespan, and to assess the effects of aging on USV and pure tone detection in quiet and noise in adult CBA/CaJ mice.
Age-related hearing loss is a major disorder in older humans assessed through behavioral measures. It is crucial to develop a reliable mouse model for ARHL using similar methodologies. The proposed study will help us understand if the CBA/CaJ mouse strain loses hearing similarly to humans for pure tones, tones of different durations, and for communication signals in quiet and in noisy environments using analogous behavioral methods.
