February 3, 2023

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Millions of ‘silent synapses’ may be key to lifelong learning: ScienceAlert

Millions of 'silent synapses' may be key to lifelong learning: ScienceAlert

Newborns need to quickly store huge amounts of new information as they learn to navigate the world. Silent synapses—the immature connections between neurons that don’t yet have neurotransmitter activity—are thought to be the devices that allow this rapid information storage early in life.

First discovered decades ago in newborn mice, these potential neural junctions were thought to disappear as the animals age. A recent study by researchers from the Massachusetts Institute of Technology in the US found that this fade may not be as extreme as initially assumed.

The team did not plan to look specifically at these potential links. Instead, they were continuing previous work on the locations of neuronal extensions called dendrites.

They got a little more than they bargained for. Not only did it take pictures of the dendrites, but countless tiny thread-like protrusions emerging from them called filamentous legs.

“The first thing we saw, which was very strange, and we didn’t expect it, was stringy legs everywhere,” Says MIT neuroscientist Mark Harnett, first author on the paper.

Usually hidden in the fluorescence glow used to illuminate the cell for imaging, the researchers used a proprietary imaging technique developed Just last year The amplified analysis is called an epitope preservation protein (eMAP).

This new imaging process uses a gel to help hold delicate cellular structures and proteins in place, allowing researchers to better study them while manipulating tissues.

viruses Green fluorescent protein is expressed in two male and two adult mice to aid in illumination of tissues relevant for imaging. Their primary visual cortex was subsequently dissected and divided into 1-millimeter slices before being incubated in eMAP monomer hydrogel solution and mounted between glass slides.

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This gives the eMAP solution time to fix the cellular architecture in place, allowing the researchers to take super-resolution images of the fluorescent dendrites.

Armed with magnified images of 2,234 dendritic protrusions, the researchers were able to see — for the first time — that the brains of adult mice had concentrations of filopedia not seen in adult mice.

What’s more, many structures have only one of the two neurotransmitter receptors projected from a mature synapse. Without the second, they were effectively “silent” junctions between neurons.

Next, the researchers asked if the adults’ silent synapses could be activated.

They showed that this was possible by releasing the neurotransmitter glutamate at the tips of filamentous filaments, producing a small electric current ten milliseconds later.

This action “untightens” synapses within minutes, stimulating the accumulation of lost receptors and allowing the filopodia to form a connection with neighboring nerve fibers.

These receptors would normally be blocked by magnesium ions, but the current liberates them, allowing the filopodia to receive a message from another neuron.

The team found that activating silent synapses was much easier than altering the activity of dendritic spines on mature neurons.

Researchers are now studying whether silent synapses are present in adult human brain tissue.

“This paper is, to my knowledge, the first real evidence that this is how it actually works in the mammalian brain,” Harnett said. Says.

“Filopodia allows the memory system to be flexible and robust. You need flexibility to get new information, but you also need stability to retain important information.”

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This paper has been published in nature.