Optogenetic tool that inhibits neural activity

Switching off specific brain regions in a laboratory animal is an important type of experiment used to better understand how the brain works. A study published in Nature Methods by researchers identified effective inhibitors of brain activity in the important animal model Drosophila melanogaster, the common vinegar fly. These new tools are enabling researchers to better understand the relationship between neural circuits and behavior, expanding our knowledge of the brain.

Neurons (brain cells) process information and control behavior by sending signals to other neurons, hormone-releasing cells and muscles. A fuller understanding of the neuronal control of behavior would accelerate the development of therapies for neurological and psychiatric disorders.

One of the ways researchers have tried to understand the neuronal control of behavior is with optogenetics, a technique that uses light-sensitive proteins to control neuronal activity in living tissue. In optogenetics, neurons are genetically modified to express light-sensitive ion channels (proteins that conduct electricity), such that light exposure may be used to activate or inhibit electrical activity.

Being able to inhibit neural circuits provides researchers the ability to determine the importance of a particular circuit in defining behavior. In view of that, researchers explored the use of anion channelrhodopsins (ACRs) from an alga species (Guillardia theta) to inhibit neural activity.

The group genetically modified flies to express ACRs, and exposed these animals to light of different colors and intensities. In one of the experiments, ACR actuation paralysed climbing flies, causing them to fall abruptly. In another, illumination of ACRs in the animals' sweet-sensing cells resulted in flies that avoided green light, as though they were avoiding the silencing of a sweet taste. At the cellular level, light actuation of ACRs produced dramatic reductions in electrical activity.

"Understanding any system is greatly aided by being able to remove components from that system and examine the resulting behaviour," explained the author. "The ACRs are the seventh generation of optogenetic inhibitors, but the first that robustly inhibit Drosophila neuronal activity. Although our study is just newly published, this new technique is already on its way to becoming key tool for behaviour analysis."

https://www.duke-nus.edu.sg/news/switching-brain

http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.4148.html