Memory relies on astrocytes, the brain’s lesser known cells.

The identity of the infected cells expressing the tetanus neurotoxin (TeNT) Δ1-GFP was established by immunofluorescence detection of astrocytic marker GFAP (a1) or the neuronal marker NeuN (a3). (a2) green fluorescence emitted by (TeNT) Δ1-GFP. In a4 the merged images are shown. Heinemann et al 2014.

When a person is expecting something, like the meal they’ve ordered at a restaurant, or when or when something captures their interest, unique electrical rhythms sweep through your brain.  These waves are called gamma oscillations and they reflect a symphony of cells, both excitatory and inhibitory, playing together in an orchestrated way. Though their role has been debated, gamma waves have been associated with higher-level brain function, and disturbances in the patterns have been tied to schizophrenia, Alzheimer’s disease, autism, epilepsy and other disorders.

Now, new research from the Salk Institute shows that little known supportive cells in the brain known as astrocytes may in fact be major players that control these waves.

In a study published in the Proceedings of the National Academy of Sciences, Salk researchers report a new, unexpected strategy to turn down gamma oscillations, by disabling not neurons but astrocytes; cells type traditionally thought to provide more of a support role in the brain. In the process, the team showed that astrocytes, and the gamma oscillations they help shape, are critical for some forms of memory.

The team state that there are hundreds of papers linking gamma oscillations with attention and memory, but they are all correlational. This is the first time researchers have been able to do a causal experiment, where they selectively block gamma oscillations and show that it has a highly specific impact on how the brain interacts with the world.

The team found that activity in the form of calcium signalling in astrocytes immediately preceded gamma oscillations in the brains of mice. This suggested that astrocytes, which use many of the same chemical signals as neurons, could be influencing these oscillations.  To test their theory, the group used a virus carrying tetanus toxin to disable the release of chemicals released selectively from astrocytes, effectively eliminating the cells’ ability to communicate with neighboring cells. Neurons were unaffected by the toxin.

After adding a chemical to trigger gamma waves in the animals’ brains, the researchers found that brain tissue with disabled astrocytes produced shorter gamma waves than in tissue containing healthy cells. And after adding three genes that would allow the researchers to selectively turn on and off the tetanus toxin in astrocytes at will, they found that gamma waves were dampened in mice whose astrocytes were blocked from signalling. Turning off the toxin reversed this effect.

The mice with the modified astrocytes seemed perfectly healthy. But after several cognitive tests, the researchers found that they failed in one major area; novel object recognition. A healthy mouse spent more time with a new item placed in its environment than it did with familiar items, as expected.

In contrast, the group’s new mutant mouse treated all objects the same.  That turned out to be a spectacular result in the sense that novel object recognition memory was not just impaired, it was gone, as if the group were deleting this one form of memory, leaving others intact.

The results were surprising, in part because astrocytes operate on a seconds timescale, or longer timescale whereas neurons signal far faster, on the millisecond scale. Because of that slower speed, no one suspected astrocytes were involved in the high-speed brain activity needed to make quick decisions.

What the team say that they feel is quite unique is the idea that astrocytes, traditionally considered only guardians and supporters of neurons and other cells, are also involved in the processing of information and in other cognitive behaviour.  It’s not that astrocytes are quick, they’re still slower than neurons, it’s that evidence suggests that astrocytes are actively supplying the right environment for gamma waves to occur, which in turn makes the brain more likely to learn and change the strength of its neuronal connections.

The behavioural result is just the tip of the iceberg.  The recognition system is hugely important as it includes recognizing other people, places, facts and things that happened in the past. With this new discovery, scientists can begin to better understand the role of gamma waves in recognition memory.

Source:  Salk Institute for Biological Studies

 

The identity of the infected cells expressing the tetanus neurotoxin (TeNT) Δ1-GFP was established by immunofluorescence detection of astrocytic marker GFAP (a1) or the neuronal marker NeuN (a3).  (a2) green fluorescence emitted by (TeNT) Δ1-GFP.  In a4 the merged images are shown.  Heinemann et al 2014.
In the hippocampus, the part of the brain that controls memory, normal astrocytes (red, a1) and neurons (blue, a3) are imaged. When the tetanus toxin is added (a2), only the astrocytes are affected (green). Panel a4 shows the other panel images superimposed. This exclusivity to the toxin allowed scientists to show that dampened activity in astrocytes interfered with new memory formation in behavioural tests. Image: Courtesy of the Salk Institute for Biological Studies

 

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