Cochlear amplification is a critical feature of the mammalian auditory system and underlies our incredible sound sensitivity, dynamic range, and frequency selectivity. This process arises from the ability of sensory receptors in the cochlea, called hair cells, to dynamically amplify and tune their response to incoming sound. Hair cells are specialized mechanoreceptors which convert mechanical information from sound waves into an electrical potential through a process termed mechano-electrical transduction (MET). MET is a necessary component of cochlear amplification, since mutations that abolish MET result in a loss of the cochlear amplifier and produce hearing loss. Current models of the MET process arose from decades of experiments performed in the hair cells of lower vertebrates or the mammalian vestibular system, which are systems that respond primarily to low frequencies. Given the evolutionary divergence of mammals from lower vertebrates, it is likely that new mechanisms in the MET process had to arise to account for the expanded frequency range and faster kinetics of the mammalian auditory system. Previously, it has been assumed that these same mechanisms translate directly to mammalian MET, but our lab has provided the first evidence that there are fundamental differences in the underlying mechanisms between mammalian and non-mammals. Thus, there is a critical need to determine the mammalian-specific mechanisms of MET regulation which forms the basis for the high hearing sensitivity unique to mammals. The cyclic adenosine monophosphate (cAMP) second messenger is one signaling pathway that has been suggested to regulate mammalian MET and is implicated in human hearing loss. However, the precise function of cAMP and it's downstream effectors in MET mechanisms and hearing function has not been explicitly tested in mammals. In this study, I will combine electrophysiology and in-vivo assays of auditory function to determine the physiological significance of cAMP signaling in MET mechanisms and hearing function in the mammalian system.
Hearing loss remains a significant unresolved public health issue. Many causes of hearing loss are associated with dysfunction of hair cell mechanotransduction (MET). A greater understanding of the mechanisms required for normal MET will lead to more effective therapeutics for human hearing loss.