High-performance genetically targetable optical neural silencing by light-driven proton pumps

Light switch for neural circuits The experimental use of microbial opsins — light-sensitive ion channels — has ushered in a revolution in neuroscience, as they make it possible to modulate the activity of genetically targeted neurons in response to exogenous light. Now, Ed Boyden and colleagues have screened archaebacteria, bacteria, plants and fungi for opsins with novel properties and have found a fundamentally new mechanism for neural control: light-driven proton pumping. Although protons are not used natively as charge carriers by neural systems, light-driven proton pumping by archaerhodopsin-3 from Halorubrum sodomense mediates powerful neural silencing in response to light. And a proton pump from the fungus Leptosphaeria maculans enables neural silencing by blue light. The use of these reagents will facilitate the shutdown of neural circuits with light as a tool for studying the role of neural circuits in behaviour and pathology. If the activity of genetically specified neurons is silenced in a temporally precise fashion, the roles of different cell classes in neural processes can be studied. Members of the class of light-driven outward proton pumps are now shown to mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) enables near 100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) 1 from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo . Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant time