How Are Memories Formed?
What physical changes occur in the brain when a memory is formed? A team of researchers from the University of Southern California has answered this question for the first time. After six years of research, they discovered that learning causes synapses—the connections between neurons—to increase in some areas and disappear in others, rather than simply changing their strength as previously believed. These changes in synapses may help explain how memories are formed and why some types of memories are stronger than others. The study was published in the Proceedings of the National Academy of Sciences.
This research became possible thanks to a new type of cell labeling and a custom-built microscope developed at the University of Southern California. The researchers also created an advanced method for tracking and archiving collected data to make their findings as accessible and reproducible as possible. Before their work, it was impossible to determine the location of a synapse in a living brain without altering its structure and function, which made it impossible to compare the brain “before” and “after” memory formation.
The researchers were able to determine the strength and location of synapses before and after learning in the brain of a living zebrafish, a species commonly used to study brain function. Zebrafish are large enough to have a fully developed brain, but small, transparent, and fast-growing enough to make live brain studies convenient. By keeping the fish alive and avoiding invasive procedures, the team was able to compare synapses in the same brain over time during learning.
The scientists trained 12-day-old fish to associate a light turning on with the heating of their heads by an infrared laser. The fish tried to avoid this unpleasant stimulus by attempting to swim away. Those that learned to associate the light with the approaching laser would wag their tails, demonstrating the desired avoidance behavior.
After five hours of training, the team was able to observe and record significant changes in the brains of these fish. In addition to this new approach, they developed new methods for modifying the fish’s DNA, allowing synaptic strength and location to be quantitatively measured using a fluorescent protein that glows under fluorescent microscopy.
“Our probes (labeled DNA fragments) can mark synapses in a living brain without altering their structure or function, which was impossible with previous tools,” the authors note.
This made it possible, using a specialized microscope developed by the USC team, to scan the brain and effectively map the location of synapses. The researchers could observe changes in living animals and obtain images of changes before and after learning in the same specimen. Previously, measurements were taken from samples collected post-mortem, so only two different brains could be compared: one trained and one untrained.
The main finding from analyzing these images: instead of simply changing the strength of existing synapses, synapses in one part of the brain were eliminated, and entirely new synapses were created in another area. The results show that changes in the number of synapses encode memories in this experiment and may help explain why negative associative memories (such as those in post-traumatic stress disorder) are so strong.
“It was believed that memory formation was mainly associated with remodeling existing synaptic connections, whereas in this study we found both the creation and elimination of synapses. At the same time, we saw only minor random changes in the strength of existing synapses. This may be because the study focused on associative memories, which are much more persistent than other types of memories and are formed in a different part of the brain, the amygdala, rather than the hippocampus, where most other memories are formed. This may be relevant to post-traumatic stress disorder, which is thought to be mediated by the formation of associative memories,” the authors say.