Temporally Precise, Genetically Targeted Optical Control of Neural Circuitry

Temporally precise, noninvasive control of neural circuitry is a long-sought goal of neuroscientists and biomedical engineers.

For this purpose, the naturally occurring algal protein Channelrhodopsin-2 (ChR2), a rapidly gated light-sensitive cation channel, was engineered by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. Blue-light illumination of neurons and other cells stably expressing ChR2 resulted in large, rapid membrane depolarization, allowing remote optical control of ionic flux and cellular voltage on the millisecond scale, with brief spikes of moderate-intensity light.

This invention will enable the optical control of the electrical and ionic milieu of neurons and other excitable cells, which might facilitate the modulation of ion channels, signal transduction, neural coding, sensory and motor processing, neuropsychiatric dysfunction and interneuron modulation of circuit dynamics.

Related Technology
The inventors have also developed a technology to optically inhibit neurons (see Stanford Dockets S06-398 and S06-398A). When combined, these inventions form a complete system for multimodal, high-speed, genetically targeted, all optical interrogation of living neural circuits.