The Role of TRP Channels in Auditory Transduction and Amplification in Drosophila

Abstract

Auditory receptor cells rely on force-gated channels to transform sound stimuli into neural activity. These primary auditory neurons form the first stage of the neural circuits that support a host of higher-order functions, such as the localization of sound or the comprehension of speech. The mechanisms of sound transduction, as well as higher-order processes such as acoustic communication during courtship, can be studied in the fruit fly Drosophila melangogaster, a model organism with a suite of powerful genetic tools. However, this work is hampered by incomplete knowledge of the components of the Drosophila auditory system and a lack of high resolution techniques for investigating their function. We used several approaches to identify candidate Drosophila central auditory neurons and developed techniques for measuring the activity of identified neurons in vivo. As an outgrowth of this work, we also developed a non-invasive method for measuring generator currents in the primary auditory neurons. Chapter 4 describes this technique and provides a basic characterization of the sensitivity of the Drosophila auditory system to sound. Determining the sensitivity of the Drosophila auditory system is necessary for understanding the neural basis of acoustic communication and has implications for the mechanism of transduction. The force-gated ion channel that transforms sound into an electrical signal has not been identified in any species. Several TRP channels have been implicated in Drosophila auditory transduction, but mechanistic studies have been hampered by the inability to record subthreshold signals from auditory receptor neurons. We recorded generator currents from primary auditory neurons to assess the roles of several TRP family members in transduction. We found that the TRPN family member NompC is not required for transduction, despite the fact that it is required for the active amplification of motion by the auditory organ. Instead, NompC is required for a process that sensitizes the transduction complex to movement and regulates the resting forces on the complex. In contrast, the TRPV channels Nanchung and Inactive are required for responses to sound, suggesting they are components of the transduction complex. Thus, transduction and active amplification are genetically separable processes in the Drosophila auditory system.