New Method To Track Neurons

Harvard Medical School (HMS) researchers have discovered a new way of looking at how the neurons in animal brains function, which might shed light on the development of neurodegenertive diseases in humans.

The approach, which uses time-lapse photography, will help show how nerve cells in the brain produce complex patterns of activity and may advance studies of neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease.

“Of course this will tell us a lot about normal brains, but in the not too distant future we would like to apply it to diseased brains as well,” said lead investigator Dr. R. Clay Reid in an HMS press release. Reid did not respond to multiple requests for comment over the last week.

Before this technique, the best method of tracking neuron responses were electrodes, which were limited to showing “impulses only in one or a very few cells at a time,” wrote Dr. David H. Hubel, HMS professor of neurobiology. “The power of [this] method is that you can see a large number of cells at once.”

The technique—called two-photon calcium imaging in vivo—was applied to the part of the brain where neural input from the eye is translated into images we see. When the animals, cats, and rats were subjected to visual stimuli of moving black and white stripes, the technique recorded images of hundreds of nerve cells firing simultaneously.

The method “allows you to see a complete circuit [of nerve cells] for the first time in its entirety,” said Reid, who is also a professor at HMS. “It gives you an immediate bird’s eye view of what the brain is doing, neuron by neuron.”

Though it has only been applied to the part of the animal brain that deals with vision, the technique is expected to be extended to other uses in the next two years, according to research fellow Kenichi Ohki, the primary developer of the project methods.

“In principle we can apply this technique for all the brain functions...such as auditory, olfactory, and [body sensation] function,” Okhi wrote in an e-mail.

In order to capture cells responses to the visual stimuli, the researchers injected clusters of cells with a substance that glows when calcium levels rise, a sign of firing neurons. Then, using a sophisticated microscope, the researchers produced time-lapse images, or successive photographs, which showed alternating groups of cells glowing: multiple clusters of firing neurons.

The technique, which generates high resolution pictures, has also revealed surprising precision of brain cell organization in the visual cortex of cats.

The new method is a combination of several previously discovered techniques, including work done by Hubel and Torsten Wiesel, who won a Nobel prize for their work. Their experiments revealed that different neurons in the visual cortex respond to different stimuli.

“There was a strict relationship between positions of neurons and functions of neurons. There was no exception,” Ohki wrote.