The frustrated zebrafish held in a virtual reality chamber did not want to swim anymore.
They "swam" in order until the virtual reality system removed the visual feedback associated with the movement. For the fish, it seemed they were drifting backwards, no matter how hard they stroked.
At first the fish struck stronger. Then they just gave up, says neuroscientist Misha Ahrens, a group leader at the Howard Hughes Medical Institute's Janelia Research Campus. "Giving up is very important for animals," he says. Without the ability to stop behavior that does not work, animals would unnecessarily lose energy.
Ahrens and his team of Janelia wanted to identify the neurons responsible for the decision to stop. The researchers observed zebrafish brain activity patterns as they struggled. But the clearest signal did not come from neurons. The cells that began to work just before the zebrafish stopped were, in fact, glial cells, long believed to play a supporting role in the brain.
The find, reported on June 20, 2019, in the journal Cell "We were excited and also very skeptical," says Ahrens. "We challenged to try and disprove it."
More than glue
Until about two decades ago, scientists thought that Glia (from the Greek for "glue") only offered support and isolation for neurons. However, recent research has begun to uncover new roles for glia in processing. Now, Ahrens, Janelia Research scientist Yu Mu and their colleagues – Davis Bennett, Mikail Rubinov and others – have shown that in zebrafish, a type of glial cells can calculate when an effort is unsuccessful.
"The original hope was that we would find the neurons that trigger this" task behavior, "says Ahrens.
Using a whole brain imaging technique developed by Janelia, the researchers were able to study all the brain cells of a fish, both the neurons and the glia. while trying to swim. The team then compared the effects of different cells on behavior.
Surprisingly, however, the team had problems identifying specific neurons that clearly influenced swimming behavior. Glia was another story, Mu says. Certain glial cells, called radial astrocytes, increased their activity in part of the brain as the animals stopped swimming.
Neurons were not completely out of the loop: every time a movement attempt failed, certain neurons turned the astrocytes around until they finally crossed a threshold and sent the command quit. This order went to another group of neurons, who then suppressed swimming.
"You could think of astrocytes as a counter to how many swimming maneuvers have failed," says Mu. It's not an easy task: to tell the fish when to give up, the glia must monitor movement attempts, make repeated mistakes and then send the message "quit" to the body.
Controlling Astrocytes, Changing Behavior
To verify the role of astrocytes, the researchers first used a laser to kill only those who were turned on continuously when giving up the fish. In fact, fish lacking these cells made longer attempts to swim than the fish whose astrocytes were left.
Next, the team created fish with astrocytes that the team could control. Turn on the astrocytes and the fish stop swimming, the team noted, even if the visual environment was not related to them. While normal fish rarely pause, fish with overactive astrocytes spend more than half their time being beaten. Taken together, these experiments confirmed that radial astrocytes actually control the decision to stop swimming, Ahrens says.
A next step for the group will be to investigate exactly how the astrocytes communicate with neurons. For example, astrocytes can release chemical messengers that affect the behavior of neurons, Mu says. "Astrocytes are like a Swiss army knife." Mu wants to find out which of her many tools she uses to stop the unproductive fight.
Astrocytes protect neurons from toxic accumulation
Yu Mu, Davis V. Bennett, Mikail Rubinov, Sujatha Narayan, Chao-Tsung Yang, Masashi Tanimoto, Brett D. Mensh, Loren L. Looger and Mischa B. Ahrens. "Radial astrocytes encode and suppress meaningless actions." Cell . Published online on June 20, 2019. DOI: 10.1016 / j.cell.2019.05.050
Thanks to Glia, frustrated fish give up, not just nerve cells (2019, June 20)
retrieved on June 21, 2019
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