Sparks of Insight
What if we could actually see what individual neurons do in real time inside a living brain?
A collaborative study between the group led by Douglas Kim, at Janelia Farm Research Campus in the USA, and Michael Orger and Sabine Renninger from the Champalimaud Neuroscience Programme (CNP), has developed a new biological tool that makes this possible.
This study, published today in the scientific journal Nature, presents new genetically encoded ‘GCaMP6’ reporters that enable researchers to optically record the complex activity dynamics in neuronal populations, which for Michael Orger “open up new and exciting possibilities in neuroscience research."
One of the hallmarks of neuronal activity is an increase in the concentration of calcium inside cells. Many genetically encoded indicators have been developed to track these changes, but until now, they suffered from low sensitivity to changes in intracellular concentration and slow response dynamics, resulting in an only a partial portrayal of the actual ongoing neural activity. “The available indicators could not reliably report activity on the level of a single action potential, which is the basic unit of communication in the nervous system, but now we can, which is a real breakthrough.” The GCaMP6 indicators are even sensitive enough to measure the communication between neurons at single synapses, so scientists can see how individual neurons process information.
In order to develop this new calcium-sensitive fluorescent protein, the group of researchers at Janelia Farm designed a high throughput system to rapidly test multiple protein variants. The lab led by Michael Orger, at the CNP, tested how effectively these proteins could report natural activity patterns in the brain, using the zebrafish as the model. “Testing these protein indicators in zebrafish is ideal. Since the fish are transparent, we are able to image neural activity anywhere in the brain without surgical intervention”, explains Michael Orger.
“In addition to having fast dynamics and high sensitivity, these new protein indicators also have the potential to be targeted to specific neuronal populations,” the author concludes, “so we can visualise the role of different types of neurons in processing information in the brain.”