Newborns need to store vast amounts of new information quickly as they learn to navigate the world. Silent synapses – the immature connections between neurons that have no neurotransmitter activity yet – are thought to be the hardware that allow this rapid information storage to occur early in life.
First discovered decades ago in newborn mice, these potential neurological intersections were thought to disappear as the animals aged. A recent study by researchers from MIT in the US has found this vanishing act might not be as extreme as initially presumed.
The team hadn’t set out to look specifically at these potential connections. Rather, they were continuing previous work on the locations of nerve-cell extensions called dendrites.
They got a little more than they bargained for. Not only did they capture images of the dendrites, but countless tiny, thread-like protrusions emerging from them called filopodia.
“The first thing we saw, which was super bizarre, and we didn’t expect, was that there were filopodia everywhere,” says MIT neuroscientist Mark Harnett, the senior author on the paper.
Usually hidden in the glare of fluorescence used to light up the cell for imaging, the researchers used a special imaging technique developed only last year called epitope-preserving magnified analysis of the proteome (eMAP).
This new imaging process uses a gel to help lock delicate cellular structures and proteins into place, allowing researchers to better study them as tissues are manipulated.
Viruses expressing a green fluorescent protein were inserted into two male and two female adult mice, to help light up the relevant tissues for imaging. Their primary visual cortex was later dissected out and divided into one-millimeter slices before being incubated in the eMAP hydrogel monomer solution and mounted between glass slides.
This gives the eMAP solution time to cement the cellular structure into place, which allowed the researchers to take super-high-resolution images of the fluorescing dendrites.
Armed with the magnified images of 2,234 dendritic protrusions, the researchers could see – for the first time – that adult mice brains had concentrations of filopedia never seen before in adult mice.
What’s more, many of the structures had only one of two neurotransmitter receptors expected of a mature, functioning synapse. Without the second, they were effectively ‘silent’ junctions between neurons.
Next, the researchers asked whether adult silent synapses could be activated.
They showed this was possible by releasing the neurotransmitter glutamate at the tips of the filopodia threads, and producing a small electrical current ten milliseconds later.
This procedure ‘unsilenced’ the synapses within minutes, stimulating the accumulation of the missing receptors and allowing the filopodia to form a connection with the neighboring nerve fibers.
These receptors are usually blocked by magnesium ions, but the current frees them, allowing the filopodia to receive a message from another neuron.
It was much easier to activate silent synapses than to change the activity of the dendritic spines on a mature neuron, the team found.
The researchers are now investigating whether silent synapses exist in adult human brain tissue.
“This paper is, as far as I know, the first real evidence that this is how it actually works in a mammalian brain,” Harnett says.
“Filopodia allow a memory system to be both flexible and robust. You need flexibility to acquire new information, but you also need stability to retain the important information.”
This paper was published in Nature.