USC team shows how memories are stored in the brain with potential impact on conditions like PTSD> News> USC Dornsife

Fish that glow; a bespoke microscope; a new way of cataloging science. After six years, researchers are producing the first snapshots of memory in a living animal. [4¼ min read]

Using software developed by USC researchers who create a map of brain synapses from a 3D microscope image, scientists compare synapse sizes and locations before and after learning to identify those that were either created or eliminated during learning.  The red line marks a boundary between regions of the brain that show total gain and total loss.  (Photo: Don Arnold.)

Using software developed by USC researchers who create a map of brain synapses from a 3D microscope image, scientists compare synapse sizes and locations before and after learning to identify those that were either created or eliminated during learning. The red line marks a boundary between regions of the brain that show total gain and total loss. (Photo: Don Arnold.)

Key takeaways:

  • Contrary to expectations, the study in larval zebrafish shows that synapses in one part of the brain are eliminated and new ones are created in another region when memories are formed.
  • These major structural changes may explain memory formation.
  • Results may also help explain why unpleasant associative memories, such as those associated with PTSD, are so robust.
  • The findings were made possible by a new type of cell label and a custom-made microscope designed at USC.

What physical changes occur in the brain when a memory is made?

A team of USC researchers has for the first time answered this question by evoking a memory in a larval zebrafish and then mapping changes in their transparent heads with brain cells that light up like Times Square on New Year’s Eve.

After six years of research, they discovered that learning causes brain synapses, the connections between neurons, to multiply in some areas and disappear in others instead of simply changing their strength, as is commonly believed. These changes in synapses can help explain how memories are formed and why certain types of memories are stronger than others.

The study was published in Proceedings of the National Academy of Sciences and was led by a team of faculties from the USC Dornsife College of Letters, Arts and Sciences and the USC Viterbi School of Engineering.

New method and tools

The study was made possible thanks to a new type of cell label and a custom-made microscope invented by USC. The researchers also developed a groundbreaking way to track and archive the data collected to make their results as accessible and reproducible as possible.

The researchers were able to determine for the first time the strength and location of synapses before and after learning took place in the brain of a live zebrafish, an animal commonly used to study brain function. By taking the unprecedented step of keeping the fish alive, they were able to compare synapses in the same brain over time, a breakthrough in neuroscience.

To create memories to measure, the research team developed new methods to make a larval zebrafish learn. They did this by training the 12-day-old fish in connecting a light that was on with being heated on its head with an infrared laser, an action they sought to avoid by swimming away. Fish, learning to connect the light to the impending laser, buzzed with their tails, indicating that they had learned. Five hours of training later, the team was able to observe and capture significant changes in the brains of these zebrafish.

Surprising results

The main takeaway: Instead of the memory causing the strength of existing synapses to change, the synapses in one part of the brain were destroyed and completely new synapses were created in another region of the brain.

“For the last 40 years, the common wisdom has been to learn by changing strength of the synapses, but that’s not what we found in this case, ”said Carl Kesselman, a computer scientist at USC Viterbi.

The results suggest that changes in the number of synapses encode memories in the experiment. This may also help explain why negative associative memories, such as those associated with PTSD, are so robust.

In addition to the results, USC Dornsife biologist Donald Arnold led a team that created new methods to change the fish’s DNA so that the strength and location of a synapse would be marked with a fluorescent protein that glows when scanned with a laser.

“Our probes can sense synapses in a living brain without changing their structure or function, which was not possible with previous tools,” Arnold said.

This allowed the specialized microscope developed by USC to scan the brain and the image where the synapses were located – without repelling the fish.

“Sometimes you try to get such a spectacular picture that you kill what you are looking at. For this experiment, we had to find the right balance between getting a picture that was good enough to get answers, but not so spectacular that we would kill the fish with photons, ”said bioengineer Scott Fraser, who has jobs at USC Dornsife and USC Viterbi and who led the development of the microscope.

The microscope allowed them to observe changes in living animals and get before and after images of the changes on the same sample. Previously, because experiments were performed on deceased samples, they could only compare two different brains, one conditioned, one not.

A group led by Kesselman developed innovative new algorithms to process and analyze hundreds of images and experiments.

The study was also unusual for its focus on making the results as transparent and reproducible as possible: All data associated with the paper is searchable and available on the publicly available website Mapping the Dynamic Synaptome.

“The USC team has set a new bar for data access, capturing every piece of data generated during the six-year study and organizing it for this research,” said Kesselman, who developed this new approach.

Added Phrase: “I truly believe this is the future of transparency in research, a new era, and USC is at the forefront.”


Researcher titles:

Don Arnold is Professor of Biological Sciences and Biomedical Engineering at USC Dornsife and USC Viterbi.

Carl Kesselman is Director of the Informatics Division at the USC Information Sciences Institute and Professor at the Daniel J. Epstein Department of Industrial and Systems Engineering at USC Viterbi.

Scott Fraser is Professor of Biological Science and Biomedical Engineering at USC Dornsife and USC Viterbi.

About the study

The ongoing study represents the latest interdisciplinary collaboration at USC with researchers at the USC Michelson Center for Convergent Bioscience, USC Dornsife, USC Viterbi and the Keck School of Medicine at USC. Launched in 2016, the center brings together a diverse network of leading scientists and engineers under one roof thanks to a generous $ 50 million gift from orthopedic spinal surgeon, inventor and philanthropist Gary K. Michelson and his wife, Alya Michelson.

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