Abundant silent synapses in the adult brain

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Millions of “silent synapses,” or immature connections between neurons that are inactive until called upon to aid in the formation of new memories, have been shown to exist in the adult brain, according to MIT neuroscientists.

Until now, it was believed that silent synapses were only present in the early stages of brain development when they assisted the brain in absorbing new information. However, the most recent MIT study found that around 30% of all synapses in the cortex of adult mice’s brains are silent.

According to the researchers, the existence of these silent synapses may contribute to the understanding of how the adult brain can continuously create new memories and learn new information without having to alter its already-existing conventional synapses.

“These silent synapses are looking for new connections, and when important new information is presented, connections between the relevant neurons are strengthened. This lets the brain create new memories without overwriting the important memories stored in mature synapses, which are harder to change,” says Dimitra Vardalaki, an MIT graduate student and the lead author of the new study.

Silent synapses were predominantly found in the developing brains of mice and other animals when they were originally discovered by scientists decades ago. These synapses are thought to assist the brain in collecting the enormous amounts of information that young children require to learn about their environment and how to interact with it. These synapses in mice were thought to vanish by the time they were 12 days old (equivalent to the first months of human life). Silent synapses were predominantly found in the developing brains of mice and other animals when they were originally discovered by scientists decades ago. These synapses are thought to assist the brain in collecting the enormous amounts of information that young children require to learn about their environment and how to interact with it. These synapses in mice were thought to vanish by the time they were 12 days old (equivalent to the first months of human life).

However, some neuroscientists have proposed that silent synapses may endure into adulthood and aid in the creation of new memories. Animal models of addiction, which are believed to be primarily a condition of abnormal learning, provide evidence for this.

It has also been theorised by Stefano Fusi and Larry Abbott of Columbia University that neurons must exhibit a variety of different plasticity mechanisms in order to explain how brains effectively learn new information and store it in long-term memory. In this scenario, some synapses must form or change quickly to create new memories, while others must maintain long-term memories by remaining considerably more stable.

The MIT researchers did not particularly seek out silent synapses for the new study. Instead, they were exploring a fascinating result from a prior experiment in Harnett’s lab. In that study, the researchers demonstrated how dendrites, which resemble antennae and protrude from neurons, can process synaptic input differently depending on where they are located within a single neuron.

To determine if this could help explain the variations in their behavior, the researchers attempted to quantify the neurotransmitter receptors in various dendritic branches as part of that study. They achieved this using a method known as eMAP (epitope-preserving Magnified Analysis of the Proteome), which Chung created. By physically expanding a tissue sample and labeling particular proteins within it, researchers can use this method to produce images with an extremely high level of resolution.

They made a surprising finding while they were performing that imaging. The first thing, which was quite unusual and unanticipated, was that there were filopodia everywhere, according to Harnett.

Thin membrane protrusions called filopodia, which extend from dendrites, had been observed before, but neuroscientists were unsure of their exact functions. This is due to the fact that filopodia are so small that they are difficult to detect using typical imaging techniques.

Following this discovery, the MIT team used the eMAP technology to search for filopodia in additional regions of the adult brain. To their amazement, they discovered filopodia at a level 10 times higher than previously observed in the mouse visual cortex and other regions of the brain. Additionally, they discovered that filopodia lacked AMPA receptors but did have NMDA receptors, which are neurotransmitter receptors.

A typical active synapse has both of these types of receptors, which bind the neurotransmitter glutamate. NMDA receptors normally require cooperation with AMPA receptors to pass signals because NMDA receptors are blocked by magnesium ions at the normal resting potential of neurons. Thus, when AMPA receptors are not present, synapses that have only NMDA receptors cannot pass along an electric current and are referred to as “silent.”

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