A New Synaptic Tool Helps ‘See’ Millions of Brain Cells in Mice

Scientists from Johns Hopkins University Medicine have created a new tool that can track connections among brain cells in mice. The new tool helps scientists to take a look inside the animals' brains and brain activities in synapses. The study is published in the journal eLife.

The main aim of the study was to see how learning and memory occur in mice. As a result of the study, the team has found that when the animals’ whiskers tweak, it's actually an indicator for learning.

Seeing the brain activity on such a massive scale was a step up for the scientists. Richard Huganir, Ph.D., Bloomberg Distinguished Professor of Neuroscience and Psychological and Brain Sciences at The Johns Hopkins University and director of the Department of Neuroscience at the Johns Hopkins University School of Medicine told Newswise, "It was science fiction to be able to image nearly every synapse in the brain and watch a change in behavior."

According to the team, prior to their tool, clearly seeing brain activity was similar to looking up at the night sky and stars with bare eyes. Austin Graves, Ph.D., instructor of neuroscience at the Johns Hopkin University School of Medicine said that now, "it’s like we can see and track each of the stars at the same time."

How do they do it? 

The connection between brain cells is based on neurons and synapses. And the space in between is less than a micron thick, which is almost a tenth of the width of a human hair. We're talking about an incredibly tiny and hard-to-image area. 

This area is where the magic happens; these spaces act much like a highway for passing molecules and proteins from one brain cell to the next. The team's study shows that this is also the main location for learning in the brain and where memories are stored. Grave says that "these receptors are the functional machinery of language between neurons."

While there have been other studies that focus on mapping the brain, they haven't been able to screen the entire brain at this scale. To be able to get a clearer image from the inside of the brain, researchers inserted the GRIA1 gene into the DNA of the mice. The genetically engineered mice then produced a green glowing tag on all AMPA glutamate proteins. This helped the team see that when neurons amp up their signals, they produce more AMPA glutamate proteins, resulting in brighter green tags. Thus, the team could pinpoint nearly all neurons that are more likely to communicate with other neurons.

The team then tweaked a whisker on each mouse and tracked the glowing synapses with high-powered microscopes. As a result, they came across 600,000 glowing synapses.

But since the new system generated massive data, the team worked with computational scientists to use AI and machine learning to create algorithms that can automatically detect the bright green synapses and their changing behavior over time. The revolutionary synaptic imaging tool helped the team go where no other team has gone before. 

According to the team, the tool could also be used to study other behaviors in mice and how their synapses change in different situations such as aging, Alzheimer’s Disease, and autism.