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Light-based method controls inhibitory neurons in macaques

by  /  12 November 2017
Stimulating inhibitory neurons in a visual brain region prevents monkeys from focusing on a line on a computer screen.
Sight unseen: Stimulating inhibitory neurons in a visual brain region prevents monkeys from focusing on a line on a computer screen.

Researchers have used a light-based method to manipulate neurons that dampen brain activity in rhesus macaques. The unpublished findings were presented today at the 2017 Society for Neuroscience annual meeting in Washington, D.C.

The method, called optogenetics, could help autism researchers identify the functions of specific sets of inhibitory neurons. It could also help connect features or symptoms, such as seizures, with aberrant firing in particular circuits.

Researchers can target excitatory neurons, which boost brain activity, in primates. But manipulating inhibitory neurons has proven tricky in monkeys, says Michael Avery, who presented the work. Avery is a former postdoctoral fellow in John Reynolds’ lab at the Salk Institute for Biological Studies in La Jolla, California.

“Every time we’ve tried to target them, it basically leaks into the excitatory neuron populations,” he says.

The ability to home in on inhibitory neurons could help researchers test a prominent theory of autism: that an imbalance in activity between excitatory and inhibitory neurons underlies the condition.

“Doing that in monkeys is really exciting because that is one thing we do not have in primate work,” says Adriana Galvan, assistant professor of neurology at Emory University in Atlanta, Georgia. Galvan was not involved in the work, but uses optogenetics in primates. “These are tools we can also potentially incorporate into our research.”

Out of line:

Researchers conduct optogenetics experiments in mice by genetically engineering them to produce light-sensitive proteins called opsins. Shining light in their brains then activates or suppresses neurons carrying the opsins. The technique has been used in mice to control social behaviors related to autism.

But genetic engineering in primates is challenging: They take longer to reproduce and reach adulthood and are difficult to modify using genetic techniques. So researchers inject primates with viruses that carry the opsin gene and deliver it to a specific region of the brain.

In the new work, the researchers first trained the monkeys to focus on a line on a computer screen and used eye-tracking technology to monitor their gaze. If the primates looked at the line, the researchers gave them a reward.

Then they injected the macaques with a virus carrying the opsin gene and a ‘promoter,’ a piece of DNA that prompts gene expression, that only works in inhibitory neurons. They targeted neurons in the visual cortex.

When the researchers shone the light, activating the inhibitory cells, the monkeys no longer looked at the line. “It makes us think we were shutting off part of that circuitry.” Avery says.

The technique could advance research on treatments, Avery says. “I think these sorts of methods are going to be really important.”

For more reports from the 2017 Society for Neuroscience annual meeting, please click here.