Neuroscientists from the Massachusetts Institute of Technology (MIT) have surprisingly found evidence that the adult brain is teeming with “silent synapses” that help to continually form new memories while also retaining the old.
Neuron
Synapses help us to store every bit of information that we gather or learn. The information, for example, could be the name of a loved one or how to do some task.
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In their case, silent synapses are immature or inactive connections between neurons. They only become active when stimulated by a signaling protein to aid in forming new memories.
The MIT research showed that roughly 30 percent of synapses in adult mice’s brain cortex are silent.
Findings from this recent study disprove the idea that silent synapses are only present in younger people. They probably explain the reason why older people continue to make new memories without completely forgetting the old ones.
The study was published in Nature.
Silent synapses and adulthood
For decades, the belief had been that silent synapses are only present during early development. Researchers found them mainly in the brains of young animals, especially mice.
These synapses were thought to aid babies and children in learning what they need to know about their environment as well as how to respond to or interact with it.
Scientists had found in mice that the silent synapses disappeared around when they become 12 days old. That age is estimated to be the same as the first months in the life of a human.
However, other researchers thought silent synapses may also be present in adults. This, they believed, makes it possible for older people to continue to form new memories.
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Neurons must exhibit diverse plasticity mechanisms for the brain to acquire new information effectively and retain what is learned in long-term memory, according to theoretical work by Columbia University’s Larry Abbott and Stefano Fusi. Some synapses would have to be formed or be easily modifiable while some others stay stable to form new memories and also retain long-term memories.
An unplanned discovery
It is interesting to note that these MIT neuroscientists were not originally looking to explore silent synapses. They were instead trying to do a follow-up on a finding from an earlier study carried out in the lab of Mark Harnett, who is the senior author of this study.
In that previous research, the team found that dendrites in a single neuron process synaptic signals in diverse ways. The location of these dendrites determines how they handle synaptic input.
The MIT researchers made use of a technique known as epitope-preserving Magnified Analysis of the Proteome (eMAP). This technique, developed by co-author Kwanghun Chung, aided in taking very high-resolution images that would be used to measure neurotransmitter receptors in dendritic branches and see if variations explained differences in behavior.
It was in the course of their imaging that the team accidentally found that previous researchers might have been looking in the wrong place for silent synapses in adult brains. The neuroscientists were amazed to find that the dendritic branches play host to numerous filopodia.
“The first thing that we saw, which was super bizarre and we didn’t expect, was that there were filopodia everywhere,” said Harnett, who is an associate professor of brain and cognitive sciences at MIT.
Filopodia are thread-like protrusions from dendrites. This was not the first time they would be seen by scientists, but their function was not known. It was difficult to know what these structures do partly because of their sizes which were too minuscule for traditional imaging methods to capture.
Using their eMAP technique, the team went on to search for filopodia in other areas of the adult brain. It was surprising to find these structures in the mouse visual cortex and other brain parts at a 10-time higher level than previously seen.
Another finding was that the silent synapses lacked AMPA receptors. There was only a different type of neurotransmitter receptors called the NMDA receptors. Both of these receptors must be present for a synapse to be active; otherwise, it remains “silent.” The two receptor types bind glutamate, a neurotransmitter.
Activating silent synapses
The MIT neuroscientists went further to confirm that the filopodia were silent synapses. They did this using a modified patch clamping technique, which helped to track electrical activity in the threadlike structures.
The researchers mimicked glutamate release from an adjacent neuron to stimulate the filopodia and then checked electrical activity in them. Glutamate could not produce any electrical signal in a filopodium unless NMDA receptors were unblocked.
According to the researchers, this provides strong evidence that filopodia embody silent synapses in the brain.
A combination of glutamate release and an electric current from the neuron’s body was shown as being capable of activating the synapses. The combined stimulation results in a buildup of AMPA receptors in silent synapses.
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These findings provide backing for the theoretical work of Abbott and Fusi. They show that there are highly-plastic synapses in the adult brain that make new memory formation possible.
The researchers in this study noted that it was a lot easier activating silent synapses than modifying matured ones.
Now, the team wants to search for evidence of similar silent synapses in the brain tissue of humans. It would also be probing whether aging, neurodegenerative disease, or other factors affect the amount or function of the synapses.
References
Filopodia are a structural substrate for silent synapses in adult neocortex
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