Scientists at MIT have developed an optogenetics technique that can lead to long-term changes in neuronal excitability by altering neuronal membrane capacitance. Unlike conventional optogenetics, which involves using light to rapidly activate ion channels on engineered neurons, the new technique relies on a light-sensitive reaction to increase the presence of conductive or insulating polymers in the cell membrane. The method creates long-term changes in neuronal excitability, and does not require continuous illumination to maintain these changes. The method is primarily intended as a research tool that can increase our understanding of the brain and neurological diseases, but it may also have therapeutic applications in the future. Optogenetics was first developed about 20 years ago. The research technique uses genetically engineering neurons to express light-sensitive ion channels and then illuminates them to provoke an immediate and rapid neuronal activation. However, while conventional optogenetics is useful, there is room for improvement. “By using light, you can either open or close these ion channels, and that in turn will excite or silence the neurons,” said Chanan Sessler, an MIT researcher involved in the study. “That allows for a fast response in real time, but it means that if you want to control these neurons, you have to be constantly illuminating them.” What if you could illuminate a neuron just once, and create a long-term change in excitability? This is the aim of this latest technique. The researchers achieved this by modifying neuronal membrane electrical capacitance. This involves engineering the neurons to express a light-sensitive protein that produces reactive oxygen species when exposed to light. During this illumination, the researchers also expose the neurons to polymer building blocks of either an insulating or conductive polymer. The reactive oxygen species help to assemble the polymer building blocks together within the cell membrane, altering its capacitance. So far, the researchers have shown that this approach leads to changes in neuronal excitability for as long as three days, which is the longest they can keep the cells alive in a dish. The approach has both research and therapeutic potential. “This new tool is designed to tune neuron excitability up and down in a light-controllable and long-term manner, which will enable scientists to directly establish the causality between the excitability of various neuron types and animal behaviors,” said Xiao Wang, another researcher involved in the study. “Future application of our approach in disease models will tell whether fine-tuning neuron excitability could help reset abnormal brain circuits to normal.” Source
