Investigation of the effects of two-pore potassium channels on high frequency signal transmission in the auditory brainstem.

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High frequency firing is a central characteristic of signal processing in the auditory brainstem circuitry involved in sound source localization. Neurons of the auditory brainstem have adapted to this requirement by expressing specialized sets of voltage-gated ion channels. These channels allow extremely precise high frequency firing, and thereby high fidelity signal transmission, as they constitute very narrow action potentials. However, another prerequisite for high frequency firing of neurons is a tightly regulated excitability, provided by two-pore-potassium channels (K2P channels). Previous studies from us and others found two K2P channel subunits prominently regulated during the postnatal development of the auditory brainstem, particularly in the critical period around the onset of hearing when high frequency firing patterns are established. The proposed project aims at elucidating the roles of these two K2P channel subunits, TREK1 and TASK5, in the regulation of neuronal excitability and subsequently ultra-precisely timed high frequency firing. Therefore, we will genetically alter the expression levels of both K2P channel subunits in the ventral cochlear nucleus and the medial nucleus of the trapezoid body of the auditory brainstem, a central relay station of this circuitry, using state-of-the-art virus-mediated gene transfer. The impact of these genetic modifications on neuronal excitability and high frequency firing will be assessed by slice electrophysiology. We expect that the results obtained in this project will enlighten the roles of these two particular K2P channel subunits in the regulation of neuronal excitability and thereby in auditory processing and sound source localization at a central auditory relay.