Researchers at MIT have developed an imaging technique that will help study exactly how electrical signals propagate through the brain, in an advance that could help us better understand Alzheimer's, epilepsy, and other brain disorders, as well as how thoughts and feelings are formed.

Brain MRIs offer important insight into how our brains work, but they can only produce crude approximations of the areas that are activated by a given stimulus. In order to unravel the minutiae of how neurons communicate and collaborate to form thoughts and feelings, we would need imaging tools with vastly improved resolutions.

Today, far from being able to tackle the 86 billion neurons in the human brain, neuroscientists must settle for studying simple organisms like worms and fish larvae (with neuron counts in the hundreds), relying on slow and cumbersome methods like implanting electrodes into brain tissue to detect electrical signals.

This, however, could soon change. The group of researchers led by Prof. Ed Boyden at MIT has built on previous work to perfect an imaging technique that provides a much fuller picture of the brain's activity. When exposed to red light, a carefully selected fluorescent protein bound to the cellular membrane of neurons reacts to electrical signals by lighting up, to reveal the exact neural path of a thought.

Boyden and team developed a sophisticated robot to select the protein among nearly 10 million candidates and 13 point mutations. The robot injected each protein candidate into a mammalian cell, grew the cells in lab dishes, and took a picture of the results, while a software component selected the compound with the best-suited characteristics, including brightness, the protein's location within the cell, and its resistance to photobleaching.

Applying the protein to zebrafish larvae, the worm Caenorhabditis elegans, as well as mouse brain tissue allowed the researchers to visualize and measure electrical activity in these organisms as it propagated through the brain. What's more, this technique can be used in tandem with so-called "optogenetic proteins" that can silence or stimulate single neurons at will. The researchers showed they could stimulate an isolated neuron in this way, and then use the fluorescent protein to follow along the path of neurons that fired in response to that single input.

Next, the researchers will be attempting to comprehensively map the brain activity of mice as they perform various tasks, with the goal to discover exactly how some neural circuits produce specific behaviors.

"We will be able to watch a neural computation happen," says Boyden. "Over the next five years or so we're going to try to solve some small brain circuits completely. Such results might take a step toward understanding what a thought or a feeling actually is."

The open-access study appears in the Feb. 26 issue of Nature Chemical Biology.

Source: MIT