By combining genetic and optic tools, optogenetics allows to control the activity of individual neurons in vivo. Optogenetics (http://optogenetics.weebly.com/index.html) was developed after the discovery of light activated cation channels and chloride pumps such as Channelrhopdopsin, Halorhodopsin and Archaerhodopsin. One of the big benefits of optogenetics is the spatial and temporal precision with which specific neurons can be selectively targeted. The strategy is to make first a construct in which the gene encoding one if this light-sensitive ion channel is put under the control of a promoter to drive its expression in the desired cells. Then you introduce this construct into, for example, a mouse’s brain or cultured cells (i.e. with the help of a virus) so the light-sensitive ion channel will be expressed in your target cells. Then, by using specific “hardware” (electrodes and fiber-optic cables) you can deliver specific light pulses to your targeted neurons in order to turn them on or off by modulating the activity of such channels. Being able to modulate specific neurons and neuronal circuits can be extremely useful to address some neurological disorders.
Keeping that in mind the laboratory of Michael Levin is using optogenetics to further study and characterize the known endogenous bioelectrical signals that are required to regulate a proper regenerative response in several animals. Thus, for example, during planarian regeneration the anterior blastema is normally depolarized by the action of endogenous H,K-ATPse activity and that triggers head regeneration. By blocking this activity, amazingly, there is a relative hyperpolarization of the blastema and that results in blocking head regeneration (http://www.ncbi.nlm.nih.gov/pubmed/21276941). Xenopus tadpoles are able to regenerate their tails. After amputation a bioelectrical hyperpolarizing signal is required to initiate tail regeneration. But Xenopus tadpoles go through a “refractory” period in which regeneration is not permitted and is accompanied by the absence of an endogenous H+-efflux. Now, in a recent paper by Adams and Tseng, the Levin lab reports the use of Archaerhodopsin-3, a light-gated proton pump to trigger tail regeneration at the “refractory” stage (http://bio.biologists.org/content/early/2013/01/11/bio.20133665.full). Through light activation of an Arch-mediated H+-efflux after tail regeneration at the “refractory” stage, the authors show a significant increase in the regenerative abilities compared to non-light-stimulated controls. Moreover this induced regenerative program activates endogenous signaling programs normally required for regeneration as those regulated by Notch1 and Msx1. The exciting consequences that these results and their further application may have in the field of regenerative medicine are obvious.