has pioneered many applications in live animals such as genetically targeted remote control in rodents in vivo, the optogenetic induction of learning in rodents, the experimental treatment of Parkinson's disease in rats, and the combination with fMRI (opto-fMRI). Other labs have pioneered the combination of ChR2 stimulation with calcium imaging for all-optical experiments, mapping of long-range and local neural circuits, ChR2 expression from a transgenic locus – directly or in the Cre-lox conditional paradigm – as well as the two-photon excitation of ChR2, permitting the activation of individual cells. In March 2013, the Brain Prize (Grete Lundbeck European Brain Research Prize) was jointly awarded to Bamberg, Boyden, Deisseroth, Hegemann, Miesenböck, and Nagel for "their invention and refinement of optogenetics". The same year, Hegemann and Nagel received the Louis-Jeantet Prize for Medicine for "the discovery of channelrhodopsin". In 2015, Boyden and Deisseroth received the Breakthrough Prize in Life Sciences and in 2020, Miesenböck, Hegemann and Nagel received the Shaw prize in Life Science and Medicine for the development of optogenetics. Designer-channelrhodopsins Channelrhodopsins are key tools in optogenetics. The C-terminal end of Channelrhodopsin-2 extends into the intracellular space and can be replaced by fluorescent proteins without affecting channel function. This kind of fusion construct can be useful to visualize the morphology of ChR2 expressing cells, i.e. simultaneously indicate which cells are tagged with FP and allow the activity to be controlled by the channelrhodopsin. Point mutations close to the retinal binding pocket have been shown to affect the biophysical properties of the channelrhodopsin, resulting in a variety of different tools. Kinetics Closing of the channel after optical activation can be substantially delayed by mutating the protein residues C128 or D156. This modification results in super-sensitive channelrhodopsins that can be opened by a blue light pulse and closed by a green or yellow light pulse (Step-function opsins). Mutating the E123 residue accelerates channel kinetics (ChETA), and the resulting ChR2 mutants have been used to spike neurons at up to 200 Hz. In general, channelrhodopsins with slow kinetics are more light-sensitive on the population level, as open channels accumulate over time even at low light levels. Photocurrent amplitude H134R and T159C mutants display increased photocurrents, and a combination of T159 and E123 (ET/TC) has slightly larger photocurrents and slightly faster kinetics than wild-type ChR2. ChIEF, a chimera and point mutant of ChR1 and ChR2, demonstrates large photocurrents, little desensitization and kinetics similar to wild-type