
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...
02/05/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
01/05/2026
January 5 2026, 18:30 (PST) NBCUniversal's Peacock to Be First Streamer to ...
19/04/2026
Blackmagic Design has announced the ATEM 4 M/E Constellation IP and ATEM 4 M/E Constellation IP Plus, two SMPTE 2110-native live production switchers. The ATEM ...
19/04/2026
Grass Valley is finding the right balance between its hardware heritage with an ...
19/04/2026
Oracle's strategy rests on the foundational strengths of Oracle Cloud Infras...
19/04/2026
Program Productions, the live sports production industry's leading crewer, i...
19/04/2026
At the 2026 NAB Show in Las Vegas, SVG sat down with Joe Scionti, Account Manage...
19/04/2026
At its 2026 NAB Show keynote event, Ross Video came out swinging with one of its...
19/04/2026
Evertz (Booth N817) is set to present new services within its evertz.io platform...
19/04/2026
Evertz (Booth N817) will showcase its IPMX-certified NUCLEUS platform alongside ...
19/04/2026
Evertz (Booth N817) is set to showcase ENX at NAB 2026, a media core platform designed to support hybrid SDI and IP infrastructures in production facilities and...
19/04/2026
Evertz (Booth N817) will introduce Studer VistaVUE Touch at NAB 2026, a control surface designed to integrate audio, video and control workflows within a custom...
19/04/2026
Evertz (Booth N817) will highlight X-CALIBER at NAB 2026, an encoding and decodi...
19/04/2026
Cobalt Digital (Booth N1340) will introduce the blueCORE family of standalone si...
19/04/2026
Chyron and Asport (Booth N2441) will demonstrate an integrated sports video work...
19/04/2026
MediaKind (Booth W1743) provided an update on its Multiview deployments at NAB S...
19/04/2026
Calrec (Booth C6907) and Grass Valley (Booth C2408) announced a long-term broadc...
19/04/2026
Oracle is bringing a multi-partner demonstration of Media over QUIC (MoQ)-based live streaming to NAB Show 2026, showcasing how independent systems from multipl...
19/04/2026
Encompass Digital Media announced an expanded partnership with Oracle Cloud Infr...
19/04/2026
The NAB Show is in full swing, and the SVG and SVG Europe editorial teams are chasing down the hottest stories from all over the Las Vegas Convention Center. He...
19/04/2026
Blackmagic Design has announced the ATEM 4 M/E Constellation IP and ATEM 4 M/E Constellation IP Plus, two SMPTE 2110-native live production switchers. The ATEM ...
19/04/2026
Now available in VST3, AU and AAX formats
Waves have recently released an update that extends their vocal-alignment plug-in's capabilities to all DAWs -...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Amagi, the agentic industry cloud platform for unified broadcast, streaming, and monetization, today announced that AccuWeather , the most trusted source of wea...
19/04/2026
Calrec (Booth:C6907) and Grass Valley (Booth: C2408) are today announcing a long-term broadcast audio technology partnership at NAB Show 2026. The companies are...
19/04/2026
Ikegami announces a further expansion to its range of on-camera viewfinders. Scheduled for introduction on Ikegamis Central Hall booth C3819 at the April 19th -...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
19/04/2026
Wuppertal April 19, 2026
Riedel's SimplyLive Solution Powers Centralized V...
19/04/2026
Wuppertal April 19, 2026
Bridge Digital and Riedel Build Campus Wide ST 2110 N...
19/04/2026
Wuppertal April 19, 2026
Riedel Showcases Next Advances in IP-Based Production at NAB 2026MediorNet HorizoN ST 2110 MultiViewer App, SmartPanel Commentary Con...
19/04/2026
Harmonic's Cloud-Native VOS Media Software Lowers Costs by Unifying Media Playout to Delivery on a Single Platform SAN JOSE, Calif. - April 19, 2026 - Harmo...
18/04/2026
MultiDyne Video & Fiber Optic Systems has begun shipping the C16-AM-12G audio mo...
18/04/2026
FOR-A America is set to detail AI functionality for its software-defined IMPULSE...
18/04/2026
Cobalt Digital and SineSix Media have announced a partnership to integrate the v...
18/04/2026
The ATSC, the broadcast standards association, is highlighting the status of the ATSC 3.0 internet protocol-based broadcast standard at the 2026 NAB Show. The e...
18/04/2026
Bolin Technology has introduced a new range of hardware for live production envi...
18/04/2026
KMH Integration is participating in the 2026 NAB Show, focusing on its AV Casti...
18/04/2026
Appear has appointed Mike Burk as vice president of business development for North America. Burk brings over two decades of experience in the broadcast and live...
18/04/2026
Skyline Communications is showcasing its DataMiner platform and the new DataMine...