Optogenetics, pioneered by Boyden and Deisseroth
43
, employs optogenetics to control
brain cell activity with visible light
44
. Certain single-celled organisms that live in hostile
environments utilize a protein similar to rhodopsin in our retina to regulate ion concentration
in response to available light. These microbial opsin proteins act as ion channels or pumpsso
as to increase excitation or inhibition. Channelrhodopsin-2 (CHR2) produces immediate
neuronal excitation in response to blue light; whereas, halorhodopsin (NpHR) produces
inhibition in response to yellow-orange light. Rhodopsins are injected via viral vectors into a
brain structure of interest. Transfection occurs in a subset of neurons and glia near the
injection site. Additional molecular biological techniques can confer light sensitivity to
specific subpopulations of cells. For example, after lentovirus delivery of the inhibitory
halorhodopsin eNpHR3 to hippocampus, use of a calmodulin kinase promoter, CaMKIIa,
leads to relatively selective light sensitivity of pyramidal neurons and dendrites. The Cre-lox
recombinant technique identifies specific stretches of DNA and splices it using Cre-recombinase. Lines of transgenic mice expressing Cre-recombinase in specific cell subtypes
have been linked to rhodopsin genes, rendering only Cre-activated cell types light sensitive.
Reduction of neuronal firing by light-induced hyperpolarization should be adaptable to
seizure control in suitable systems. Tønnesen and colleagues
45
injected a construct of
lentevirus NpHR CaMKIIαinto hippocampus of rat pups. Hippocampal slices prepared
subsequently showed pyramidal cell hyperpolarizations to orange light. Light also was able