Scientists capture a memory forming in the brain of a living fish

You most likely can remember your heartbreak vividly. When you’re reeling from the loss of a relationship that you didn’t want to end, your emotional and bodily reactions are a tangle, and throes of such agonizing heartbreak can be devastating, imprinting itself so thoroughly in your brain that it becomes impossible to forget.

However, have you ever considered what psychological changes occur in your brain while such a memory is formed?

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A team of researchers from the University of Southern California has tackled this question for the first time by creating memories in genetically engineered zebra fish and then observing the changes in their transparent heads as brain cells light up.

In other words, the researchers have produced the first snapshots of memory in a living animal in real-time.

How memories are made

While many aspects of the brain are largely unexplored, scientists believe that memories occur when certain clusters of neurons are reactivated. When you think about your first pet, for example, different groups of neurons become active. 

Scientists generally agree that the brain creates memories by changing synapses, which are the small junctions where neurons connect; however, that may not be the case.

In the latest study, published in the journal Proceedings of the National Academy of Sciences, the researchers found that learning causes brain synapses to grow in some locations and perish in others, rather than simply changing their strength, as previously thought.

And the researchers think that these changes in synapses may help explain how memories form and why some kinds of memories are more powerful than others.

Surprising results thanks to new methods

In the study, the researchers were able to assess the strength and position of synapses in the brain of a living zebrafish, which is often used to study brain function, for the first time.

Moreover, they were able to compare synapses in the same brain throughout time by keeping the fish alive with a microscope that allowed them to see changes in living creatures.

Inducing learning in larval zebrafish in order to establish memories to test meant the research team needed to devise new methods. In their breakthrough approach, the team conditioned the 12-day-old fish to associate turning on a light with getting uncomfortably heated on the head with an infrared laser, an action they attempted to avoid by swimming away. Fish that learnt to identify the light with the approaching laser would flick their tails to indicate that they had learned.

After five hours of training, the team was able to see and record significant changes in the brains of these zebrafish, discovering that, rather than memory causing changes in the strength of existing synapses, the synapses in one part of the brain were destroyed and completely new synapses were generated in another part of the brain.

The main takeaway

"For the last 40 years, the common wisdom was that you learn by changing the strength of the synapses, but that’s not what we found in this case," explained Carl Kesselman, a computer scientist at USC Viterbi, in a press release.

The researchers think that this suggests that differences in the number of synapses encode memories, and could also help explain why negative associative memories, like those related with PTSD, are so persistent.

However, one thing is certain: this study is only one piece of the puzzle of how memories form, and there are many questions remaining, like how long those memories and synaptic alterations remain in the zebra fish. Next, the researchers want to see if these findings apply to animals with larger brains.  

Study Abstract: 
Defining the structural and functional changes in the nervous system underlying learning and memory represents a major challenge for modern neuroscience. Although changes in neuronal activity following memory formation have been studied [B. F. Grewe et al., Nature 543, 670–675 (2017); M. T. Rogan, U. V. Stäubli, J. E. LeDoux, Nature 390, 604–607 (1997)], the underlying structural changes at the synapse level remain poorly understood. Here, we capture synaptic changes in the midlarval zebrafish brain that occur during associative memory formation by imaging excitatory synapses labeled with recombinant probes using selective plane illumination microscopy. Imaging the same subjects before and after classical conditioning at single-synapse resolution provides an unbiased mapping of synaptic changes accompanying memory formation. In control animals and animals that failed to learn the task, there were no significant changes in the spatial patterns of synapses in the pallium, which contains the equivalent of the mammalian amygdala and is essential for associative learning in teleost fish [M. Portavella, J. P. Vargas, B. Torres, C. Salas, Brain Res. Bull. 57, 397–399 (2002)]. In zebrafish that formed memories, we saw a dramatic increase in the number of synapses in the ventrolateral pallium, which contains neurons active during memory formation and retrieval. Concurrently, synapse loss predominated in the dorsomedial pallium. Surprisingly, we did not observe significant changes in the intensity of synaptic labeling, a proxy for synaptic strength, with memory formation in any region of the pallium. Our results suggest that memory formation due to classical conditioning is associated with reciprocal changes in synapse numbers in the pallium.