How is memory stored in the brain, and how does it potentially impact conditions such as PTSD?

What physical changes occur in the brain when memories are formed?

A team of researchers at the University of Southern California has answered this question for the first time
.

After six years of research, they have made the groundbreaking discovery that learning causes synapses (the connections between neurons) to proliferate in some areas and disappear in others, rather than just changing them, as is commonly believed strength
.

The research, published in the Proceedings of the National Academy of Sciences, was led by USC's Don Arnold, Scott E.
Fraser and Carl Kesselman
.

New methods and tools

The research was made possible thanks to a new type of cell marker and a custom microscope invented at USC
.

Before their work, it was impossible to determine the location of synapses in a living brain without modifying their structure and function, making it impossible to compare before and after memory formation
.

Through a multidisciplinary collaboration of the USC Viterbi School of Engineering and the Southern California College of Arts and Sciences, the College of Arts and Sciences team was able to determine the strength and location of the first synapses in the brain before and after learning in the living zebrafish, an animal commonly used to Study brain function
.

To create measurable memories, the team had to come up with new ways to induce learning in zebrafish larvae
.

In addition to creating this new method, Arnold, a Southern California liberal arts neuroscientist and professor of biological sciences and biomedical engineering, led a team that created new ways to alter the strength and location of synapses in fish DNA by marking a glowing fluorescent protein produced by a laser scan
.

"Our probe can label synapses in living brains without altering their structure or function, which was not possible with previous tools," Arnold said
.

This allows a specialized microscope developed by Fraser's team to scan images of the brain and where synapses are located
.

"The microscopes we built are suitable for solving this imaging challenge and extracting the knowledge we need," said Fraser, a dean of the USC Michelson Convergent Bioscience Center, a professor of biological sciences and biomedical engineering at the South University of California Viterbi Engineering, Southern California Arts and Sciences, Keck School of Medicine of USC
.

With this innovative microscope, they were able to observe changes in live animals and obtain before and after pictures of the same specimen
.

"It's ninja imaging where we sneak in without being detected," Fraser said
.

The result is hundreds of images and experiments that need to be processed and analyzed
.
A third group, along with Kesselman, computer scientists at the USC Michelson Center for Convergent Biosciences and the William H.
Keck USC Viterbi Professor of Engineering, developed innovative new algorithms that make it all possible while tracking Large and complex experiments take time to conduct investigations
.

surprising result

When analyzing these images, the main takeaway was that instead of memories changing the strength of existing synapses, synapses in one part of the brain were destroyed and entirely new ones were created in another area of ​​the brain
.

"For the past 40 years, it has been widely believed that you can learn by changing the strength of synapses," said Daniel J.
"But that's not what we found in this case," said Kesselman, a Daniel J.
Epstein professor in the Department of Industrial and Systems Engineering
.

"This is the best result we could possibly get," Arnold said, "because we saw dramatic changes in the number of synapses -- some disappearing, some forming, and we saw it in a very distinct part of the brain
.
" This The theory is that synapses change their strength
.
But to my surprise, we saw a push-pull phenomenon, and we didn't see a change in synaptic strength
.
"

The findings suggest that changes in the number of synapses experimentally encode memories, which may help explain why negative associative memories, such as those associated with post-traumatic stress disorder (PTSD), are so powerful
.

"It has long been thought that memory formation primarily involves remodeling of existing synaptic connections," Arnold said, "However, in this study, we found synapse formation and elimination, but we only saw existing synaptic connections.
Tiny, random changes in synaptic strength
.
" This may be because the study focused on associative memory, which is stronger than other memories and is formed in a different part of the brain -- the amygdala, while most other memories are in formed in the hippocampus
.
This may one day be related to post-traumatic stress disorder (PTSD), which is thought to be mediated through the formation of associative memories
.
"

An unusual aspect of the paper and related research is its focus on making the findings as transparent and reproducible as possible, making every piece of data relevant to the paper searchable and available to anyone on a publicly available website.
Scientist, Mapping Dynamic Synaptome (http://synapse.
isrd.
isi.
edu)
.
Accessibility of all data and code is necessary to replicate scientific results, however, access to all data used to generate papers is rarely achieved
.
For example, recent studies have shown that only 20% of cancer studies are reproducible because data are not available
.

"The USC team set a new standard for data access, with every piece of data produced during the six-year survey period captured and organized for this study," said Kesselman, who designed this new paradigm
.
"We tackled this problem from the start, creating a comprehensive system for data sharing and data analysis
.
It was useful when we were doing experiments, because the team had ready access to the data, and it would guide those who want to use it in the future.
Our work people
.
"

"I truly believe this is the future of research transparency, a new era, and USC is ahead of the curve," Fraser said
.

article title

Regional synapse gain & loss accompany memory formation in larval zebrafish