How scientists uncovered memory's hidden architecture New structural hallmarks of memory storage discovered by Scripps Research could lead to treatments for memory loss.
March 21, 2025
LA JOLLA, CA Using cutting-edge genetic tools, 3D electron microscopy, and artificial intelligence, Scripps Research scientists and colleagues have uncovered key structural hallmarks of long-term memory, called an engram. Their study, published in Science on March 20, 2025, paves the way for future advances in treating memory loss and other cognitive impairments associated with aging and neurodegenerative diseases.
Our work leverages recent technological developments across multiple fields, says Marco Uytiepo, a Scripps Research graduate student and the study's lead author. We used high-resolution 3D imaging to reveal the intricate architecture of brain circuits that store memory traces with unprecedented detail. Since analyzing these images with conventional computer programs could take years, we relied heavily on AI algorithms to accelerate data processing by several orders of magnitude.
Uytiepo and his colleagues focused on the hippocampus, a brain region crucial for learning and memory in both animals and humans. They used mouse models to label and identify neurons activated during a specific learning task and, at nanometer-scale resolution, then reconstructed their synaptic connections (the junctions where neurons communicate).
We hoped to uncover something interesting since no similar approaches had been implemented before, says Anton Maximov, professor of neuroscience and the study's senior author. What we did not expect was that our findings would challenge two long-standing dogmas.
At neuronal synapses, chemical signals are typically transmitted from a single nerve terminal a swollen region of an axon filled with vesicles that secrete these signals to a single postsynaptic site on the dendrite of a receiving cell. Many previous studies (using lower-resolution optical imaging methods) have suggested that learning requires a bulk increase in synapse number. However, Maximov's team found that this is not always the case the total number and arrangement of isolated synapses remained unchanged after memory formation. Instead, neurons allocated to an engram expanded their connectivity through multi-synaptic boutons (MSBs) specialized axonal terminals that simultaneously signal to up to six different dendrites rather than just one. These MSBs were not only more abundant along the axons of activated neurons but also structurally more complex.
Secondly, Maximov's team discovered that engram neurons in adjacent hippocampal regions do not preferentially connect with each other, counter to what is widely believed in the field. Instead, the expansion of their network through MSBs resulted in the recruitment of other neurons that were not engaged during learning. Moreover, the researchers found that engram neurons exhibited fine-scale alterations in the architecture of their individual synapses, including changes in intracellular organelles such as mitochondria and smooth endoplasmic reticulum. Additionally, these neurons displayed enhanced interactions with astrocytes glial cells that regulate synaptic function and provide metabolic support.
Researchers now aim to determine whether similar mechanisms operate in other brain circuits and whether their dysfunction contributes to memory loss. Furthermore, MSBs have emerged as promising therapeutic targets.
We are excited about the possibility of targeting MSBs with drugs to develop new and effective treatments for memory disorders, says Maximov. However, achieving this goal will require designing new tools to dissect the molecular composition of MSBs, which remains entirely unexplored. We are already making progress in this direction, but much work still lies ahead.
As part of this effort, the researchers are also continuing to refine their AI pipelines to improve the efficiency and accuracy of analyzing large-scale imaging data.
This study was conducted in collaboration with the National Center for Microscopy and Imaging Research (NCMIR) at UC San Diego, directed by Distinguished Professor of Neurosciences Mark H. Ellisman. As an NIH BRAIN Initiative National Resource for Technology Integration and Dissemination, NCMIR provides cutting-edge imaging tools that advance neuroscience research.
We feel incredibly fortunate to have joined forces with Mark and his team, says Maximov. Their deep knowledge, technical expertise, and access to state-of-the-art microscopes were instrumental to our success.
This work was supported by funding from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and The Brain Research Through Advancing Innovative Neurotechnologies Initiative, or The BRAIN Initiative .
In addition to Uytiepo, Ellisman and Maximov, authors of the study, Synaptic architecture of a memory engram in the mouse hippocampus, include Yongchuan Zhu, Katherine Chou, Filip Souza Polli, Elise Zhao, Danielle Luu, Lyanne Chang, Dong Yang, Tsz Ching Ma, Mingi Kim, Yuting Zhang, Grant Walton, Tom Quach, Luca Patapoutian, Arya Shahbazi, Yuxuan Zhang, Elizabeth Beutter, Weiheng Zhang, Brian Dong, Aureliano Khoury, Alton Gu, Elle McCue and Lisa Stowers of Scripps; and Eric Bushong, Keun-Young Kim and Matthias Haberl of UCSD.
Neuroscience Maximov, Anton
Most recent headlines
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
30/05/2026
Zero in on one that says yes (and no)
Andy Marken May 29, 2026
0 Comments
Hero image courtesy of Deposit Photos
For content creators the most difficu...
29/05/2026
With InfoComm 2026 just weeks away, NDI is giving attendees plenty of reasons to...
29/05/2026
Reaffirming a partnership that has defined Canadian sports broadcasting since 19...
29/05/2026
Mobile/tablet is No. 2 device for watching TV, suggesting that the sports-production industry needs to take another look at the format
Ring Digital's Sprin...
29/05/2026
Berliner Ensemble, one of Berlin's five major theater companies, has expande...
29/05/2026
Solid State Logic will showcase its new compact, fly-away TCA Tour audio product...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, passed away last month on April 12 ...
29/05/2026
Paramount+ will be the English-language U.S. home for Barclays Women's Super...
29/05/2026
Further strengthening its virtualisation strategy to fully support broadcasters ...
29/05/2026
Swiss broadcaster Canal Alpha has deployed Harmonic's award-winning, software-based XOS Advanced Media Processor to modernize playout operations across cant...
29/05/2026
PTZOptics will showcase a new generation of intelligent video workflows at InfoComm 2026, June 17-19, Las Vegas. Visitors to booth N8227 will see how PTZOptics ...
29/05/2026
Arizona's Family has launched the Arizona's Family Sports (AZFS) streaming app, a new direct-to-consumer destination for live, local sports. The app is ...
29/05/2026
Starting in 2027, DAZN will be the exclusive home of The Canadian Football Leagu...
29/05/2026
Comcast Business has detailed the advanced network infrastructure it has deploye...
29/05/2026
In two-day event, leaders from academia and industry explored solutions to chall...
29/05/2026
The Basketball Tournament (TBT), now entering their 13th year of competition, ha...
29/05/2026
Roku has launched FOX One as a Premium Subscription on The Roku Channel in the U.S. Roku customers can now subscribe to FOX One using their Roku account for liv...
29/05/2026
In its sixth year, the broadcaster's coverage has become a global brand and ...
29/05/2026
Ratings Roundup is a rundown of recent ratings news and is derived from press re...
29/05/2026
The days are getting longer, the temperatures are rising, and playlists are filling up for the season. With summer around the corner, Spotify's global edito...
29/05/2026
New retro-inspired MPC announced
There are few devices that have gained the status held by Akai Pro's MPC range, and in recent years, the company have s...
29/05/2026
Save up to 30 on acclaimed titles
Following a successful launch at Superbooth 2026, Bjooks have revealed that they will be continuing the Kickstarter campa...
29/05/2026
Binaural monitoring application improved
Genelec have just released an update that brings some powerful new features to their HRTF-based binaural headphone ...
29/05/2026
6 June 2026 at SAE Institute, London, UK
IMSTA FESTA 2026 is almost upon us, with some of the biggest names in pro-audio set to descend upon SAE Institute i...
29/05/2026
Gerald (Jerry) Pierce, a pioneering technologist who helped shape the digital transformation of the motion picture industry, died April 12, 2026, at his home in...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Comparing 5 AI Video Enhancers for Restoring Old Video Quality
Kate Luvis May 29, 2026
0 Comments
Digitizing VHS, MiniDV, and other legacy formats doe...
29/05/2026
Studio Hamburg Builds New Post Pipeline with DaVinci Resolve Studio
Brie Clayton May 29, 2026
0 Comments
Workflow replaces a patchwork of legacy tools...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
29/05/2026
At the Intersection of Music and Dance, an Epic Collaboration Boston Conservatory musicians and dancers found creative parallels in their recent performance o...
29/05/2026
May 29 2026, 09:00 (PDT) Dolby and rednote Bring More Immersive Storytelling to...
29/05/2026
Something fundamental has shifted in how people consume media. Audiences aren't abandoning television or radio content; they're just expanding how, wher...
29/05/2026
Youtube exclusive special drops today
Watch now
UKTV today announces another e...
29/05/2026
Back to All News
The Official Trailer of Physical 100 Italy, on Netflix From Se...
29/05/2026
At just 20 years old, Sean Melia from Summerhill Co. Meath has been revealed as the winner of Super Garden 2026. Sean is the youngest ever contestant and winner...
29/05/2026
Experimental HIV vaccine achieves a long-sought goal In a first for the field, all non-human primates given a new series of vaccines generated antibodies capabl...
How scientists uncovered memory's hidden architecture New structural hallmarks of memory storage discovered by Scripps Research could lead to treatments for memory loss. 
