Astrocytes Help Brain Establish Long-Lasting Memories, Animal Study Finds
Astrocytes, long considered to be passive elements in the brain, are required to establish long-lasting memories, according to a study in mice.
Astrocytes tagged with green fluorescent antibody. Image credit: Instituto de Medicina Molecular João Lobo Antunes / António Pinto-Duarte.
The brain’s neurons rely on speedy electrical signals to communicate throughout the brain and release neurotransmitters, but astrocytes instead generate signals of calcium and release substances known as gliotransmitters, some of them chemically similar to neurotransmitters.
The classical view was that astrocytes’ function was mostly to provide support to the more active neurons, helping transport nutrients, clean up molecular debris, and hold neurons in place.
More recently, researchers found that these cells might play other, more active, roles in the brain through the release of gliotransmitters but these remain largely mysterious.
In 2014, Salk Institute’s Professor Terrence Sejnowski and colleagues showed that disabling the release of gliotransmitters in astrocytes turned down a type of electrical rhythm known as a gamma oscillation, important for cognitive skills.
In that study, when the authors tested the learning and memory skills of mice with disabled astrocytes, they found deficits that were restricted to their capacity to discriminate novelty.
In the new study, Professor Sejnowski’s team looked for the first time at the longer-term memory of mice with disrupted astrocytes.
The scientists used genetically engineered animals lacking a receptor called type 2 inositol 1,4,5-trisphosphate (IP3R2), which astrocytes rely on to release calcium for communication.
They tested the mice with three different types of learning and memory challenges, including interacting with a novel object and finding the exit in a maze.
In each case, mice lacking IP3R2 showed the same ability to learn as normal mice.
Moreover, when tested in the 24-48 hours after each initial learning process, the mice with disrupted astrocytes could still retain the information — finding their way through the maze, for example.
The results were in line with what had been seen in prior studies. However, when the group waited another 2 to 4 weeks and retested the trained mice, they saw large differences: the mice missing the receptor performed much worse, making more than twice as many errors when completing the maze.
“After a few-weeks delay, normal mice actually performed better than they did right after training, because their brain had gone through a process of memory consolidation. The mice lacking the IP3R2 receptor performed much worse,” said Salk Institute postdoctoral researcher António Pinto-Duarte, first author of the study.
The results were published in the journal GLIA.
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António Pinto-Duarte et al. Impairments in remote memory caused by the lack of Type 2 IP3 receptors. GLIA, published online July 26, 2019; doi: 10.1002/glia.23679