Tinnitus Alleviation by Activation of Dendritic IA Channels

Chronic tinnitus, a constant ringing in the ear, is a major cause of disability in modern society. In particular, hearing loss-induced tinnitus is often present with various comorbidities including insomnia, deficits in attention, anxiety and depression which severely affect the quality of life. Unfortunately, there are limited therapeutic treatments to alleviate tinnitus. Currently, it is known that tinnitus is involved in neuronal excitation/inhibition (E/I) balance which is largely modulated by ion channels and receptors along the auditory pathway. Here, we propose a strategy for tinnitus treatment by activating A-type potassium channels (IA) localized along the dendrites of cortical neurons. Our preliminary data in animals with hearing loss-induced tinnitus indicates a down-regulation of IA channels in auditory cortical neurons. These channels can shape neuronal excitability and therefore the circuits underlying tinnitus. We will employ advanced techniques including two-photon calcium imaging, glutamate uncaging, virus transfusion, and tinnitus animal models; these tools will identify the functional role of IA on tinnitus. This result will provide a thorough mechanistic account of tinnitus and insight into the possible pharmaceutical benefit of an IA enhancer to alleviate tinnitus.