February 4, 2023

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Your Brain Is Home To Millions Of Incomplete Connections (And That's A Good Thing)

Your Brain Is Home To Millions Of Incomplete Connections (And That’s A Good Thing)

Thanks to these “silent synapses,” we can constantly form new memories and learn new things, without replacing existing synapses.

You may have heard about synapses at some point. A synapse essentially connects neurons and allows information to be transmitted. But there are also so-called “silent synapses”: patchy connections between inactive neurons. Until recently, it was thought that only children’s brains house silent synapses. But now it appears that the adult brain also has millions of incomplete connections. And there is no reason to worry about that.

Silent clamps
It’s been decades since scientists first encountered silent synapses. They find it mainly in the brains of young mice and other small animals. For this reason, it was thought that during early development, these synapses help the brain collect the massive amounts of information babies need to learn more about their environment. Silent synapses are thought to disappear in mice around 12 days of age – the equivalent of the first months of human life. However, some neuroscientists have suggested that adults also have silent synapses. But the conclusive evidence has so far remained undiscovered.

dendrites
In the new study, the research team didn’t look specifically at silent synapses. Instead, they followed up on an interesting finding from an earlier study. In that study, the scientists showed that within a single neuron, dendrites (see box) can process synaptic input in different ways, depending on their location. As part of that study, the researchers attempted to measure neurotransmitters in different dendritic branches to see if that would help explain the differences in observed behavior.

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More about bifurcations
Neurons in the human brain receive electrical signals from thousands of other cells. The long extensions of nerve cells – the dendrites – conduct electrical impulses to the nerve cell and enable these cells to communicate with each other. Thus, dendrites play an important role in information absorption.

The researchers made a surprising discovery. “The first thing we saw was very strange and we didn’t expect it at all,” researcher Mark Harnett recalled. “We’ve seen string legs everywhere.”

filopodia
Filopodia are thin, pointed outgrowths of bifurcations. Neuroscientists had seen them before, but weren’t quite sure what their purpose was. This is because the string legs are very small. This makes them difficult to visualize with conventional imaging techniques, but they can now be detected with another advanced technique (eMAP). After the surprising observation, the team went on to search for string legs in the brains of adult mice. To their surprise, they found filopodia in the mouse’s visual cortex, as well as in other parts of the brain. In addition, they discovered that the legs of nematodes contain NMDA receptors, but not AMPA receptors.

active clamps
The latter is particularly striking. A typical active synapse needs both types of receptors to bind to the neurotransmitter glutamate (indispensable in our information processing). NMDA receptors normally interact with AMPA receptors to transmit signals. Thus, when AMPA receptors are missing, synapses containing only NMDA receptors cannot pass an electric current and are therefore referred to as ‘silent’.

Silent clamps
Does this mean that these thread legs are actually silent clamps? To verify this, the team used advanced technology that allowed them to measure the electrical activity produced by a single filopodium. They stimulated this by simulating the release of the neurotransmitter glutamate from a neighboring neuron. Using this technique, the researchers found that glutamate will not generate an electrical signal in the filopodium unless NMDA receptors are experimentally unblocked. And that’s interesting. Because this strengthens the theory that the string legs are silent clamps.

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memories
The researchers found that in adult mice, about 30 percent of all synapses in the cerebral cortex are silent synapses. This means that the adult brain has millions of incomplete connections. Why are they? It is hypothesized that mice—and perhaps humans too—can continually form new memories and learn new things thanks to these silent synapses, without overwriting existing ones.

New information
This means that silent synapses are actually constantly looking for new connections. Then, when important new information is presented, connections between relevant neurons are strengthened. This allows the brain to create new memories without overwriting important memories stored in mature synapses, which are also difficult to alter. The researchers discovered that turning silent synapses into active synapses is much easier than changing mature synapses. “The synapses in the adult brain have a much higher threshold,” Harnett explains. “Maybe because you don’t want already-formed memories to be constantly overwritten. On the other hand, filopodia can be used to form new memories.”

first clue
Overall, the researchers showed, the adult brain has highly plastic synapses that can be manipulated to form new memories. “Our study is, as far as I know, the first real evidence of this,” says Harnett. Filopodia makes the memory system flexible and robust. You need flexibility to gain new information, but you also need stability to retain important information.”

The next step is to show that human brain tissue also has such silent synapses. They also hope to study whether the number or function of these synapses is affected by factors such as aging or neurodegenerative diseases. “It’s quite possible that as flexibility changes, new information becomes more difficult to absorb,” Harnett speculates. Follow-up research should clarify this further.

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