Live fish brain study reveals surprises about where and how memories form

Scientists at the University of Southern California (USC) have managed to image the formation of memories inside the brains of live fish in real time. And the results were intriguing – synapses were seen forming in one part of the brain while disappearing from another, in contrast to just strengthening as previously thought.

Synapses are tiny gaps between the branches of neighboring neurons in the brain, and it’s widely accepted that they play a key role in memory formation. The more regularly a particular synapse is used, the stronger it becomes, reinforcing a memory associated with that synapse. But the new study uncovered more of the story.

The USC researchers conducted their work using zebrafish, which are commonly used for neuroscience studies. Not only do the fish have brains that are similar to humans but simpler, they also have conveniently transparent heads, giving scientists an almost literal window into the inner workings of the brain.

Synapses are normally too tiny to image directly, so the researchers used a few new tricks to highlight them. They genetically engineered the fish to have fluorescent synapses, then imaged them using a new type of laser microscope that uses lower levels of light, to reduce damage to the tissue. Using this setup, the team imaged the fish brains both before and after a memory was formed to see how the synapses changed.

To induce memory formation, the scientists conditioned the fish to associate two stimuli, one neutral and one unpleasant. The animals’ heads were warmed with an infrared laser, which they found unpleasant and would cause them to flick their tails to swim away. The researchers paired this heat with another light, and within a few hours of training the fish began flicking their tails in response to the light alone, indicating they’d formed an associative memory between the light and the heat.

The researchers were surprised by what they observed in the brains of the fish. Rather than just seeing the synapses strengthening, as expected, they noticed that one brain region was forming new synapses, while another was eliminating them. The team says that this suggests that memories are encoded through changes in the number of synapses instead.

“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,” says Carl Kesselman, an author of the study.

The team says that more work needs to be conducted to confirm the role that synapse generation and loss plays in memory formation. Future work will probe further by attempting to erase synapses from zebrafish or mice to test whether associative memories will also be erased – which might one day lead to new treatments for PTSD and addiction, the researchers claim.

The study was published in the journal PNAS.

Sources: USC, The Conversation