Combining the physics of light with genetics to control brain cells may sound a bit like science fiction. Nonetheless, scientists did just that in mice recently, in a pioneering proof-of-concept study to record the real-life firing of neurons.
Neurons, the cells of the nervous system, communicate by transmitting chemical signals to each other through junctions called synapses. This “synaptic transmission” of messages is a vital function of the brain and the spinal cord – and studying it in living animals is a tricky business. Researchers have had to use artificial conditions that don’t capture the real-life environment of neurons.
Now, scientists from École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland have recorded synaptic transmission in a live animal for the first time. As reported in the scientific journal Neuron, they achieved this by a new approach that combines the physics of light with genetics.
Optogenetics: controlling neurons with light
Known as “optogenetics”, the technique uses light to precisely control the activity of specific neurons in living, even moving, animals in real time. Such precision is necessary for studying the hundreds of different neuron types, and for understanding higher brain functions such as thought, behaviour, language, memory – or even mental disorders.
The method involves genetic modification of neurons so that they produce a light-sensitive protein. Sitting on the outside of the cell, the protein acts as an electrical channel – a kind of gate. When light is shone on the cell, the channel opens and allows ions to flow into the neuron, creating an electrical charge. It’s a bit like a battery being charged by a solar cell.
The electrical charge changes the voltage balance of the neuron and – if strong enough – generates an explosive electrical signal. So, in a nutshell, optogenetics enables scientists to control the activity of neurons by switching a light on and off.
Recording neuronal transmissions
At EPFL’s Brain Mind Institute, Aurélie Pala and Carl Petersen used optogenetics to stimulate single neurons of anesthetised mice. When Pala shone blue light on neurons that contained the light-sensitive protein, the neurons fired signals. At the same time, she measured electrical signals in neighbouring neurons using microelectrodes that can record small voltage changes across a neuron’s membrane.
This way, the researchers were able to record and analyse synaptic transmissions from light-sensitive neurons to some of their neighbours: small connector neurons called “interneurons”. In addition, they used an advanced imaging technique (two-photon microscopy – see Combining methods in “Going beyond the limits of light”) that allowed them to look deep into the brain of the live mouse and identify the type of each interneuron they were studying.
“This is a proof-of-concept study,” says Pala, who received her PhD for the work. “Nonetheless, we think that we can use optogenetics to put together a larger picture of connectivity between other types of neurons in other areas of the brain.”
Adapted from article by Nik Papageorgiou, EPFL Mediacom