Aravanis et al. measured a 50% reduction in fiber-coupled optical power through of brain tissue penetration that increased to 90% after 1 mm of tissue depth using a 20 mW laser diode system.15 Laser systems penetrate through tissue with greater efficiency due to their low angle of incidence and high numerical aperture (see Sec. 2.3). The light exiting this multimodal fiber outputs is considerably high at and spreads at an angle of 32 deg with a numerical aperture of 0.37. Neuronal activation is achievable at least 1.4 mm from the fiber tip, where optical power is at least and covers a 1 mm diameter cross-section. With such high levels of tissue penetration and optical power, laser-based systems have proven useful in early optogenetic experiments. The first experiments demonstrating neuronal activation through a light source were performed in 1971 by Richard Fork using a 488 nm blue laser light at Bell laboratories.22 Their experiments required an extremely high level of irradiance (), achievable through laser systems, to activate native abdominal ganglia of marine mollusks. Karl Deisseroth, who coined the term “optogenetics,” first demonstrated millisecond-timescale activity control of Channelrhodopsin-2 (ChR-2) transfected mammalian cells using a 300 W xenon lamp in 2005.16 Since then, several light delivery devices have been introduced, including light-emitting diodes (LEDs), organic LEDs (OLEDs), liquid crystal displays (LCDs), halogen lights, and arc lamps. More recent systems have adopted LED systems over laser systems due to benefits in price, instrument size, beam stability, and high frequency temporal precision.23 Despite the high power intensities achievable through laser-based systems, sufficient levels to activate ChR-2 proteins with 470 nm photostimulation are modest, with the minimum spiking irradiance being between 0.1 and (or to ).24 At intensities , ChR-2 response falls below 10%.25 High-intensity light sources, such as arc lamps16,26 and lasers,15,27,28,29 can achieve these optical outputs, as well as many LEDs;30–32 however, their function is limited to single-point illumination and whole-field illumination. OLEDs and LCDs, on the other hand, produce greater spatial resolution on two-dimensional arrays, but fall short on providing adequate irradiance for photoactivation (on the order of , three orders of magnitude too low to activate ChR-2).33 Many newer optogenetic systems rely on LED light such as that developed by Clements et al.23 Their LED optogenetic system delivers adequate photostimulation to ChR-2 transfected neurons in mice to induce a freeze behavioral response, with peak light output from the device measuring at 29.6 mW through a 465 nm LED. With a total time lag of 328 microseconds from the trigger to 90% peak output, this LED-based device ensures the reliable temporal precision necessary for optogenetic stimulation parameters.