Despite all the neuroscience advances we’ve made in the last century, our understanding of how memories are made in the brain is still a flummoxing mystery. After six years of grueling experiments, however, we might finally have some answers.
For the first time ever, scientists have taken snapshots of living animal brains as they form memories, revealing the synapses (connections between neurons) that are forged—and severed—in the brain in real time. The findings, published Monday in the journal PNAS, lay the groundwork for helping us learn more about why some memories are stronger than others, and how we may be able to treat “pathological memories” that lead to conditions like PTSD.
The new study focuses around observations made in zebrafish—neuroscientists’ favorite organism. “Zebrafish are capable of very sophisticated behavior,” Donald Arnold, a biomedical engineer at the University of Southern California, told The Daily Beast.” And at an early age, “the fish essentially have no skull. They’re almost perfectly transparent. So it’s very easy to image them.”
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The research team conditioned 14-day-old zebrafish to associate a light turning on with having an infrared laser beamed at their heads—an uncomfortably hot experience they desperately wanted to avoid. When the lights flickered on, the fish would start wagging their tails, indicating they knew the heat was coming on and they needed to start moving fast to avoid it—confirmation that a memory was made.
At the same time, Arnold and his colleagues observed the brains of these zebrafish using new methods pioneered for this study. The zebrafish were genetically engineered to make fluorescent proteins that helped the researchers visualize synapses as they formed and disappeared. A new kind of microscope was developed to specifically observe synaptic interactions inside zebrafish brains. And the team wrote new kinds of software that could properly take these brain scans and create 3D images that showed the precise locations and intensity of synaptic activity.
Altogether, this enabled the team to watch the zebrafish brains light up like Christmas trees while memories were made. It was the first time this process was observed in living animals; previous experiments had only ever been conducted on dead specimens.
Over the last several decades, neuroscientists thought that memories caused the strength of synapses to change, But what the USC authors saw in the zebrafish was quite different: synapses in one part of the brain were destroyed while completely new ones were formed in other parts. This means memories are encoded simply through the changes in the number of synapses in the brain.
“The interesting thing about this is that now we've actually seen synapses that form or that disappeared during memory formation,” said Arnold. “So, if it were possible to really characterize these things in, say, in a human, it might be possible to go in and actually change them, and in that way, erase the memory,” like those associated with traumatic experiences.
Arnold was quick to point out that any notion that we’ll be able to Eternal Sunshine our brains to purge them of unwanted memories is just science fiction at this point—“way, way down the road.” But the new findings do suggest “the idea that you can go in and change synapses and get rid of a pathological memory is definitely possible,” he said. “It’s definitely easier to conceive of going in and erasing new synapses, versus trying to readjust all the synapses to their original state [before memory formation].”
But first, the authors want to see whether erasing new synapses in zebrafish actually does affect memory, and home in on how synapses in different regions of the brain work together to tell the fish how it should respond and make decisions in the presence of stimuli. If those investigations go well, the next step will be figuring out how to replicate the findings in mammals like mice, and then eventually humans. Perhaps then we can start talking seriously about how to get rid of a memory with the snip of a synapse.
