Role of the ClC-a channel in Drosophila behavior and physiology

The circadian oscillator of Drosophila is comprised of approximately 250 clock neurons that express a set of molecular signatures, including clock genes, which through negative feedback loops coordinate oscillation of transcription and translation of other genes and proteins. A subgroup of clock neurons, called ventral lateral neurons (LNvs) is characterized by the expression of the neuropeptide Pigment Dispersing Factor (PDF). LNvs play a fundamental role in the control of alertness and are essential for the regulation of sleep/wake behavior via a yet not fully understood neuronal circuit. Previous work from our laboratory has identified ClC-a, a voltage-dependent chloride channel, as a potential key element in the physiological regulation of LNvs. This channel has not been explored in the Drosophila adult neurons. Therefore, the main objective of this project is to characterize the roles of neuronal CIC-a and its mechanism of action. Our findings indicate that downregulation of ClC-a in LNvs disrupts neuropeptide trafficking and impairs clock output. Additional behavioral analyses suggest that ClC-a may be involved in detection of sensory stimuli, such as light and mechanical stimuli. To further investigate the physiological basis of these behavioral effects, we are currently performing whole-cell patch clamp recordings in LNvs.