VALIDATION OF OPTOGENETIC PROTEIN EXPRESSION IN THE DORSAL COCHLEAR NUCLEUS – MOLECULAR BASIS FOR IN VITRO AND IN VIVO INVESTIGATION OF TINNITUS IN MICE
Optogenetics, cochlear nucleus, tinnitus
Tinnitus ("ringing of the ears") is the perception of a phantom sound in the absence of a corresponding physical stimulus. It is not clear yet what are the mechanisms involved on tinnitus and how exactly it starts and/or becomes chronic. There are studies demonstrating the relation between noise-induced hearing loss and an increased neural synchrony, excitability and spontaneous firing rate (e.g. Seki and Eggermont, 2003; Yang et al, 2011; Manzoor et al, 2013) as triggers for homeostatic plasticity, tonotopic reorganization of the auditory cortex, and then, tinnitus. The use of optogenetic proteins like channelrhodopsins and archaerhodopsins can allow us to study the cellular mechanisms behind such altered neuronal firing, and in the longer run be correlated to noise-induced tinnitus models. On this study we examined the expression of optogenetic proteins (Channelrhodopsin 2 - ChR2; and Archaerhodopsin-3 - Arch3) targeting neurons expressing Calmoduline Kinase II alpha (CaMKIIa) promoter using local virus delivery. Using a specific promoter will increase the likelihood of identifying expression in specific neuronal populations (for example, fusiform cells) in the dorsal cochlear nucleus in mice. By applying these optogenetic tools we aim to provide tools to test tinnitus theories by producing an increased firing rate, trying to mimic tinnitus; or inhibiting increased spontaneous firing rate on animals with noise-induced tinnitus, trying to eliminate it.