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Silenced synapses to make room for memories

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MIT neuroscientists have discovered that the adult brain contains millions of “silent synapses,” immature connections between neurons that lie dormant until they’re recruited to help form new memories. Until now, silent synapses were thought to be present only during early development, when they help the brain learn new information it is exposed to early in life. However, the new MIT study has revealed that in adult mice, about 30 percent of all synapses in the cerebral cortex are silent. The existence of these silent synapses may help explain how the adult brain is able to continuously form new memories and learn new things without having to changeexisting conventional synapses, the researchers say.

 

“These silent synapses are looking for new connections, and when important new information is presented, the connections between the affected neurons are strengthened. This allows the brain to create new memories without overwriting important ones stored in mature synapses, which are more difficult to modify,” explains Dimitra Vardalaki, lead author of the new study.

The research team tried to measure the neurotransmitter receptors in the different dendritic branches (branches of the neuron that carry the nerve signal towards the nucleus of the cell), to do so they used a technique called eMAP (epitope-preserving Magnified Analysis of the Proteome /enlarged proteome analysis with epitope conservation), developed by Chung. With this technique, researchers can physically expand a tissue sample making it possible to obtain very high resolution images.

The strange case of the filipods

As they ran these pictures, they made a startling discovery. “The first thing we saw, which was super bizarre and we didn’t expect, was that there were filopodia everywhere,” says one of the authors. Filopodia, in essence, are thin protrusions – which in the case of neurons extend from dendrites – used by cells to probe the surrounding environment. They are, very, very small and therefore difficult to study and detect with traditional imaging techniques. The researchers took advantage of the eMAP technique, developed by Chung, to begin to better study these further tiny branches.

 

MIT scientists have been trying to locate filopodia in other areas of brain tissue. Surprisingly, they also found them in the mouse visual cortex and other parts of the brain. They then decided to monitor the electrical activity generated by individual filopodia as they stimulated them by mimicking the release of the neurotransmitter glutamate from a nearby neuron. Using this technique, the researchers found that glutamate did not generate any electrical signals in the input-receiving phyllopodium. However, if the glutamate receptors were unblocked experimentally, then the electrical signal was generated in the small filament. This lends strong support to the theory that the filopodia represent silent, but when needed, synapses within the brain.

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Furthermore, after this discovery, scientists hypothesize that reactivating silent synapses is much easier and more useful than trying to get already active but mature synapses to work. “If you start from an already functional synapse, you don’t get the same plasticity,” explains Harnett.

The research team’s next goal is to find these silent synapses in human brain tissue. They also hope to understand whether the number or function of these synapses is influenced by factors such as aging or neurodegenerative diseases . “It is entirely possible that by changing the amount and, therefore, the flexibility of the memory system, it becomes much more difficult to change one’s behaviors and habits or to incorporate new information,” the scientists say. “One could also imagine finding some of the molecular actors involved in the filopodia and trying to manipulate some of these elements to try to restore a flexible memory as we age.”

  • Filopodia are a structural substrate for silent synapses in adult neocortex. (nature.com)
 

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