Williams, R. H., Chen, T. M., Tsunematsu, T., Yamanaka, A., & Kilduff, T. S. (2013, 9-13 November). Optogenetic silencing of hypocretin/orexin neurons using transgenic expression of a light-driven proton pump. Paper presented at the Neuroscience 2013, San Diego, CA.
Hypocretin/orexin (Hcrt) neurons are integral for maintenance of arousal. Although optogenetic tools have been used to investigate Hcrt circuitry, prolonged inhibition of Hcrt-mediated behavior has been problematic. We generated orexin/Arch transgenic mice in which the prepro-orexin promoter drives expression of eGFP as well as modified archaerhodopsin-3 (Arch), a neuronal silencer activated by yellow light. Arch encodes a light-activated proton pump that causes cellular hyperpolarization and produces more substantial currents at lower irradiance levels than halorhodopsin. Thus, Arch may be better suited for long-term circuit inhibition, and may serve as an important tool for deciphering the role of Hcrt signaling in the maintenance of wakefulness.