A new 'off' switch for neurons
Scientists have found a way to silence individual neurons, using optogenetics, which previously could only turn on neurons. Optogenetics is a method used by neuroscientists to study how specific neurons work. They shine LED or laser light on genetically modified neurons (light-activated) that function as ion channels, which then turn on the neurons in which these ion channels are expressed.
HHMI scientist Karl Deisseroth and his colleagues at Stanford University published their new findings April 25, 2014 in the journal Science. “We’re excited about this increased light sensitivity of inhibition in part because we think it will greatly enhance work in large-brained organisms like rats and primates,” he says.
First discovered in unicellular green algae in 2002, channelrhodopsins function as photoreceptors that guide the microorganisms’ movements in response to light. In a landmark 2005 study, Deisseroth and his colleagues described a method for expressing the light-sensitive proteins in mouse neurons.
By shining a pulse of blue light on those neurons, the researchers showed they could reliably induce the ion channel at channelrhodopsin’s core to open up, allowing positively charged ions to rush into the cell and trigger action potentials. Channelrhodopsins have since been used in hundreds of research projects investigating the neurobiology of everything from cell dynamics to cognitive functions.
A few years later came the deployment of halorhodopsins, light-sensitive proteins selective for the negatively charged ion chloride. These proteins, derived from halobacteria, provided researchers with a tool for the light-controlled inactivation of neurons.
A major limitation of these proteins, however, is their inefficiency. Unlike channelrhodopsin, halorhodopsin is an ion pump, meaning that only one chloride ion moves across the neuron’s membrane per photon of light. “What that translates into is you get partial inhibition,” Deisseroth says. “You can inhibit neurons, but in the living animal it’s not always complete.”