The Pause Button Inside The Brain

Using optogenetics, researchers in Japan have demonstrated how the activity of specific neurons in the brain allow mice to prioritize their responses to the environment.

AsianScientist (May 21, 2018) – Pauses in the firing of certain neurons help the brain prioritize different stimuli, according to a study published in eLife.

Changing our behavior based on unexpected cues from our environment is an essential part of survival. The ability to drop what you’re doing when circumstances demand it could mean the difference between avoiding a speeding vehicle or getting hit by it.

In this study, researchers at the Okinawa Institute of Science and Technology (OIST), Japan, investigated nerve cells in the striatum, a brain region involved in movement and motivation. Here, nerve cells called cholinergic interneurons (CINs) are in a near-constant state of activity, releasing a chemical called acetylcholine every time they fire. But if the brain gets an unexpected stimulus from outside the body—for example, a startling sound—the CINs will briefly stop firing.

“The purpose of these pauses is a mystery,” said senior author Professor Jeff Wickens of OIST. “We wanted to know what these pauses do.”

To find out, his team manipulated CIN activity with a method known as optogenetics. They used a virus to replace sections of these neurons’ DNA with genes encoding for light-sensitive ion channels. Optical filaments were then implanted into the striatum of mice.

By shining a laser beam into the cell along the filaments, the researchers could switch the CINs into active or inactive mode as the mice moved around their cage. This allowed the researchers to generate pauses in CIN firing at will.

Subsequently, the researchers used electrodes inserted into single nerve cells to record the electrical impulses generated during the pauses. Previous studies recorded from outside of neurons, which can only generate limited information about the impulses they generate. To get a clear recording of electrical potential, the team needed direct measurements from inside the cell.

“You have to make a hole inside an individual cell and attach a probe without damaging it,” said Wickens. “It is extremely fine work that Dr. Zucca has perfected.”

When they generated the pauses in CIN activity, the researchers observed a knock-on effect on the neurons that CINs connect to—neurons called spiny projection neurons, which in turn send signals from the striatum to the rest of the brain.

During the pauses, because spiny projection neurons received lower stimulation from CINs, they were less likely to fire as well. These pauses, then, give interrupting events priority by effectively muting the striatum’s output signals.

The changes in CIN activity may be a mechanism for controlling how animals respond to stimuli from their environment, said Wickens.

“[For example], this mechanism might regulate how an animal stops eating when it hears an unfamiliar sound,” he suggested. “The CINs only make up one percent of cells in the striatum, but they have a huge influence. “They’re important in making changes in behavior, and play a part in movement disorders like Parkinson’s disease when they malfunction.”

The researchers now plan to explore the phenomenon in greater detail.

“Next, we’d like to see if this pause is happening everywhere in the striatum at the same time, or if it’s limited to specific locations,” Wickens added.

The article can be found at Zucca et al. (2018) Pauses in Cholinergic Interneuron Firing Exert an Inhibitory Control on Striatal Output in vivo.


Source: Okinawa Institute of Science and Technology Graduate University.
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