What if you change your mind with the flip of a light switch? Over the past decade, optogenetics has become an important component of neuroscience research. By introducing genes that code for fast light-activated proteins (opsins) into a specific cell-type, researchers can shine a certain color of light onto living tissue to activate these opsins and examine how those specific cells’ activity modulates behavior in real-time. For example, light-activation of specific neurons in the motor cortex of a mouse causes it to only make right turns, but otherwise behave normally when the light is off. Thus, optogenetics is a great tool to see how neural activity is coordinated with behavior.
What if you could stop a seizure with light? In a recent paper from the laboratory of Ivan Soltesz, Ph.D. at UC Irvine, optogenetics was used to treat epileptic mice. Epilepsy is a disorder of recurrent spontaneous seizures, which result from abnormal, excessive, or hyper-synchronous neuronal activity. It is hypothesized that if you can reduce this excitable state, epilepsies may be able to be controlled. In this study, mice were genetically modified to express the light-activated protein called halorhodopsin, which inhibits neurons so they cannot fire action potentials, in excitatory principle cells of the hippocampus. The researchers used an optical fiber to deliver a laser light into the hippocampus of mice that had form of epilepsy called temporal lobe epilepsy (TLE). Within five seconds of laser light activation, seizure duration was significantly reduced by half! Seizure control was also achieved when excitatory opsins called channelrhodopsin were selectively expressed in a subpopulation of GABAergic inhibitory cells that make up <5% of neurons in the hippocampus. The results of this study show that spontaneous seizures can be terminated by directly inhibiting overly excited seizing neurons or by activating inhibitory neurons within a specific brain region.
This study is significant because it opens the door to developing novel optogenetic treatments for epilepsy. Modulating the activity of specific neurons in a temporally and spatially selective manner is better than the brain-wide effect that seizure-reducing medications offers. While we are perhaps a long way from treating epileptic people, a clinical approach based on the principles established in this study may overcome many of the side effects of current treatment options. Hopefully, future improvements in gene therapy methods and light stimulation will be able to help overcome these obstacles and pave the way for a whole new class of optogenetics-based therapies in patients with epilepsy and other neurological disorders.
~Krook-Magnuson, E., Armstrong, C., Oijala, M., & Soltesz, I. (2013). On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nature Communications, 4 DOI:10.1038/ncomms2376 Images adapted from Andrzej Wojcicki/Science Photo Library/Corbis and made by Kate Jones.