For the first time ever, neuroscientists have observed memory-forming molecules travel around the brain of a living animal. The unprecedented breakthrough is shedding light on how nerve cells make memories.


Prior to being able to recall — or more accurately, reconstruct — a memory, it has to be encoded and stored in the brain. It's a complicated and dynamic process involving changes to molecular structures which alter synaptic transmissions between neurons. But watching this process in action is easier said than done.


Fluorescent Green Glow

Indeed, neurons are incredibly sensitive to any kind of disruption, so observing them as they go about their memory-making work in living brain cells is no easy task. To overcome this, and to peer deep into neurons without harming them, researchers at Albert Einstein College of Medicine at Yeshiva University developed a mouse model in which they fluorescently tagged all molecules of messenger RNA (mRNA) that code for beta-actin protein (proteins involved in cell structure and integrity).


Beta-actin proteins are an essential structural protein found in large amounts in brain neurons and are considered a key player in making memories. mRNA is a large group of RNA molecules that copy DNA's genetic information and translate it into the proteins that make life possible.

Here's the video of the process in action:

Masking and Unmasking

To make this incredible video, the researchers stimulated neurons in the hippocampus of mice — the place where memories are made and stored. They watched fluorescently glowing beta-actin mRNA molecules form in the nuclei of neurons and travel within dendrites, the neuron's branched projections.


As they watched this, the scientists realized that mRNA in neurons have developed an ingenious and never-before-seen strategy for controlling how memory-forming proteins do their job. It's a novel process they describe as "masking" and "unmasking" — a process allowing beta-actin protein to be synthesized at specific times and places and in specific amounts.


"This observation that neurons selectively activate protein synthesis and then shut it off fits perfectly with how we think memories are made," noted lead researcher Robert Singer in a statement. "Frequent stimulation of the neuron would make mRNA available in frequent, controlled bursts, causing beta-actin protein to accumulate precisely where it's needed to strengthen the synapse."

"It's noteworthy that we were able to develop this mouse without having to use an artificial gene or other interventions that might have disrupted neurons and called our findings into question," said Singer.


Read the entire study at Science: "Visualization of Dynamics of Single Endogenous mRNA Labeled in Live Mouse."

Image credit: Albert Einstein College of Medicine.