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
North America Stories
08/01/2026
At CFP Semifinals, ESPN Again Flexes Its Operational Muscle With 20+ MegaCast Vi...
08/01/2026
SVG Students To Watch: Sophie Fowler, University of OregonThe Portland product has honed her skills as a producer, director, and TD at Quack VideoBy Brandon Cos...
08/01/2026
Follow the Money, Episode 3: Inside the Sports-Media Biz With Sam McCleery and K...
08/01/2026
SVG New Sponsor Spotlight: Qualstar's Jeff Sengpiehl on the Enduring Power a...
08/01/2026
Legendary February: Production Leaders at NBC Sports Pull Back the Curtain on Ol...
08/01/2026
The Hollywood Professional Association (HPA) today announced several updates to its Board of Directors. As part of HPA's annual governance cycle, new leader...
08/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
08/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
08/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
08/01/2026
Spain's national public broadcaster, RTVE, has upgraded one of its main television production facilities in Madrid with the installation of two Alfalite NEO...
08/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
08/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
08/01/2026
Maxon's new release of Cinebench features performance enhancements and adds support for the latest Nvidia and AMD GPUs as well as Apple Silicon.
Maxon is t...
08/01/2026
Zixi, the industry leader in IP-based video transport and orchestration, today announced the appointment of Heather Mellish as Vice President, Global Sales.
In...
08/01/2026
Pebble, the leading automation, content management and integrated channel specialist, has provided a complete update of its installation at Canal Sur in Spain. ...
08/01/2026
iWedia, a global leader in software solutions for connected TV devices, proudly announces the success of its collaboration with Panasonic on the Z95B OLED TV, o...
08/01/2026
Secuoya Chile, a leading provider of television content creation and supporting services, has invested in Ikegami UHK-X600 and UHL-X40 broadcast cameras as the ...
08/01/2026
Kiloview, a global leader in AV-over-IP solutions, will showcase its latest innovations at ISE 2026, highlighting the continued evolution of its complete, light...
08/01/2026
iWedia, a global leader in software solutions for connected TV devices, and Realtek, a leading global SoC design house, today announced the next phase of their ...
08/01/2026
CJP Broadcast has completed a new pitch-side media installation for Cinderford RFC, creating a flexible production setup that supports match coverage, coaching ...
08/01/2026
PlayBox Neo further drives momentum in Playout, Streaming, Media Management and Delivery
"With a brand new year at PlayBox Neo already off to a flying start, I...
08/01/2026
Boston Conservatory at Berklee Presents Second Annual Commercial Dance BFA Conce...
08/01/2026
Back to All News
New Korean Series Beauty in the Beast' (WT) in Production...
08/01/2026
The next universal technology since the smartphone is on the horizon - and it ma...
08/01/2026
In the rolling hills of Berkeley, California, an AI agent is supporting high-stakes physics experiments at the Advanced Light Source (ALS) particle accelerator....
08/01/2026
NVIDIA is wrapping up a big week at the CES trade show with a set of GeForce NOW...
07/01/2026
SVG Summit 2025: All General Sessions Now Available To Watch on SVG PLAYThe SVG Summit celebrated its 20th edition with a loaded agendaBy Brandon Costa, Directo...
07/01/2026
NBCU's Brings Rinkside Live' and Courtside Live' Features to Peaco...
07/01/2026
NASA's Space Launch System rocket carrying the Orion spacecraft launches on the Artemis I flight test, Wednesday, Nov. 16, 2022, from Launch Complex 39B at ...
07/01/2026
For the first time ever, new C' variants allow international users to interoperate with U.S. personnel via NSA-certified cryptography....
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Share Share by:
Copy link
Facebook
X
Whatsapp
Pinterest
Flipboard...
07/01/2026
Back to All News
The Trailer of Paparazzi King: The 5-Episode Docuseries Coming...
07/01/2026
Back to All News
Netflix Supports Warner Bros. Discovery Board's Commitment...
07/01/2026
Back to All News
What Next? Netflix Reveals Series, Films and Games Coming in 2026
Entertainment
07 January 2026
Global
Link copied to clipboard
Download ...
07/01/2026
AI has transformed retail and consumer packaged goods (CPG) operations, enhancin...
How scientists uncovered memory's hidden architecture New structural hallmarks of memory storage discovered by Scripps Research could lead to treatments for memory loss. 
