Summary: Astrocytes, star-shaped non-neuronal cells, serve as active gatekeepers of long-term memory stability. By identifying a key scaffolding protein called ankyrin-2 (Ank2), the team unmasked a molecular pipeline showing how astrocytes physically embrace and stabilize specialized memory-storing “engram” neurons. When this astrocytic mechanism is disrupted, initial memory formation remains perfect, but the long-term stabilization process completely collapses, causing memories to fade within weeks.
Key Facts
- The Ank2 Molecular Switch: The researchers isolated ankyrin-2 (Ank2), a structural protein highly expressed in astrocytes, as the core master regulator determining memory duration.
- The Recall Disconnect: To test the protein’s function, the team engineered knockout mice lacking Ank2 specifically within their astrocytes. Immediately after learning, these mice presented completely normal locomotor control, social behaviors, and baseline memory. However, when tested two weeks later, their remote memory recall was profoundly impaired. This proves that creating a memory and preserving it over time rely on entirely separate biological systems.
- Fraying the Engram Contact: Without the Ank2 protein, astrocytes developed significantly simpler, stunted physical branches. Consequently, they failed to establish essential physical contacts with nearby engram neurons, the specialized cell clusters that act as the physical storage lockers for memories.
- Synaptic Potentiation Failure: This lack of physical touch selectively blocked the maintenance of long-term potentiation (LTP), the persistent strengthening of synapses that forms the cellular basis of memory, while leaving standard day-to-day synaptic transmission untouched.
- The Calcium Signaling Breakdown: At a deeper level, the team unmasked that Ank2 acts as a gatekeeper for brain-derived neurotrophic factor (BDNF) signaling through the astrocytic TrkB.T1 receptor and $IP_3R2$-mediated calcium signaling. When Ank2 is deleted, internal calcium signaling weakens, leaving the star-shaped cell unable to structurally reshape itself around nearby memory circuits.
- Optogenetic Restoration with Opto-T1: To prove that astrocytes actively drive this stability, the team built a light-activated genetic tool called Opto-T1. By flashing light to selectively trigger the TrkB.T1 pathway in astrocytes, they induced immediate cellular remodeling, successfully sustained long-term potentiation, and heavily boosted long-term memory persistence without altering short-term recall.
- A New Clinical Framework: Because Ank2 mutations are heavily implicated in autism spectrum disorder, intellectual disabilities, and epilepsy, these findings provide a vital new lens for clinical medicine. It suggests that hidden astrocytic defects, rather than primary neuronal death, may be a primary driver behind age-related cognitive decline and memory disorders.
Source: Institute of Basic Science
Some memories remain with us for years, shaping how we learn from experience and adapt to the world around us. Others disappear quickly, even when they once seemed important. Although scientists have long studied how memories are formed in the brain, far less is known about what allows certain memories to persist over time.
A research team led by Dr. KOH Wuhyun at the Center for Memory and Glioscience within the Institute for Basic Science (IBS), together with researchers at the Korea Brain Research Institute (KBRI), has now discovered that astrocytes play a critical role in this process. Astrocytes are star-shaped cells in the brain that have traditionally been considered support cells for neurons.
The study shows that these cells actively help determine whether memories can be maintained over long periods of time, revealing a previously unknown mechanism that supports long-term memory persistence.
For decades, memory research has focused primarily on neurons because they process and transmit information throughout the brain. While scientists have made significant progress in understanding how memories are initially formed, the biological processes that preserve memories over time have remained poorly understood. Long-lasting memory is essential for learning, accumulating experience, and normal cognitive function, making it important to understand how the brain stabilizes memory after learning has taken place.
The researchers identified a protein called ankyrin-2 (Ank2), which is highly expressed in astrocytes, as a key regulator of memory persistence. To determine whether astrocytes directly contribute to long-term memory maintenance, they developed mice in which Ank2 was selectively removed from astrocytes. Although these mice showed normal locomotion, anxiety-like behavior, sociability, and recent memory immediately after learning, they exhibited significantly impaired remote memory two weeks later.
These findings demonstrate that forming a memory and maintaining that memory over time rely on distinct biological mechanisms, expanding the long-standing neuron-centered understanding of how memories are stored in the brain.
The researchers further found that astrocytes lacking Ank2 developed much simpler cellular structures and formed significantly fewer physical contacts with nearby engram neuronsโthe specialized neurons that store specific memories. These learning-dependent contacts are thought to help stabilize the neural circuits that preserve memories over long periods of time. In addition, the maintenance of long-term potentiation (LTP), a cellular process widely associated with long-term memory, was selectively impaired while normal synaptic transmission remained intact. Together, these findings indicate that astrocytes actively help stabilize the neural circuits required for preserving memories long after they are formed.
The team next investigated how Ank2 supports this process at the molecular level. They found that Ank2 is required for brain-derived neurotrophic factor (BDNF) signaling through the astrocytic TrkB.T1 receptor and IP3R2-mediated calcium signaling. When Ank2 was absent, calcium signaling weakened, astrocytes failed to undergo normal structural remodeling, and their ability to maintain contacts with memory-encoding neurons was compromised.
The researchers further demonstrated that hippocampal BDNF infusion normally strengthens long-term memory persistence, but this effect disappeared when astrocytic Ank2 was deleted, showing that Ank2 is essential for BDNF-dependent memory stabilization.
To determine whether astrocytic BDNF signaling alone is sufficient to enhance memory, the team developed a new optogenetic tool called Opto-T1, which selectively activates TrkB.T1 signaling in astrocytes using light. Activation of this pathway promoted astrocyte remodeling, maintained long-term potentiation, and significantly enhanced remote memory without affecting recent memory.
These experiments demonstrate that selectively stimulating astrocytes is sufficient to strengthen memory persistence, identifying astrocytes as active regulators rather than passive supporters of long-term memory.
โOur findings show that astrocytes are not passive support cells, but active regulators that determine how long memories last,โ said Dr. KOH Wuhyun, corresponding author of the study. โBy identifying Ank2 as a key regulator of astrocyte remodeling and BDNF signaling, we have uncovered a new mechanism that helps stabilize long-term memories and opens new avenues for understanding and potentially treating memory disorders.โ
Beyond advancing our understanding of memory, the findings suggest that astrocytic dysfunction may contribute to cognitive decline and neurological disorders involving impaired memory. Because Ank2 has also been implicated in autism spectrum disorder, intellectual disability, and epilepsy, the researchers believe the study provides a new framework for understanding how astrocytes regulate long-term memory and contribute to neurological diseases.
Key Questions Answered:
A: For decades, neurons got all the credit because they function like the brain’s electrical wiring system. However, this study proves that astrocytes, star-shaped cells long dismissed as basic cellular support glue, act as active structural managers of your mind. Think of neurons as the initial bricklayers of a memory, while astrocytes act as the concrete sealant. They physically grow and wrap their branch-like arms around memory-storing neurons to insulate and stabilize their connections, preventing your oldest memories from fading away.
A: The South Korean research team designed a brilliant experiment where they selectively removed a specific scaffolding protein called Ank2 from the astrocytes of mice. Right after a training session, these modified mice performed flawlessly, their short-term memory was completely intact, proving they had no trouble forming the memory. But when researchers tested them again two weeks later, their ability to recall what they had learned had completely dissolved. This isolated a critical biological boundary: creating a memory trace is a separate neuronal task, but maintaining it long-term requires active structural help from astrocytes.
A: Opto-T1 is a cutting-edge optogenetic tool engineered by the research team that allows scientists to control the behavior of star-shaped astrocytes using focused beams of light. By targeting a specialized receptor called TrkB.T1, flashing this laser instantly tells the astrocytes to expand their branches and lock down nearby memory circuits. In lab models, this single intervention heavily boosted the lifespan of distant memories. Because astrocytic breakdown is increasingly linked to conditions like Alzheimer’s, autism, and cognitive decline, Opto-T1 proves that finding ways to stimulate these star-shaped cells could lead to revolutionary new treatments for memory loss.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience and memory research news
Author:ย William Suh
Source:ย Institute for Basic Science
Contact:ย William Suh โ Institute for Basic Science
Image:ย The image is credited to Institute for Basic Science
Original Research:ย Open access.
โAstrocytic Ankyrin-2 Enables Memory Persistence in the Mouse Hippocampusโ by Hayoung Kim (๊นํ์), Jiwoon Lim (์์ง์ด), Jooyoung Kim (๊น์ฃผ์), Erva Ozkan (Erva รzkan), Gyu Hyun Kim (๊น๊ทํ), HyoJin Park (๋ฐํจ์ง), Mingu Gordon Park (๋ฐ๋ฏผ๊ตฌ), Bitna Joo (์ฃผ๋น๋), Sangkyu Lee (์ด์๊ท), Kea Joo Lee (์ด๊ณ์ฃผ), Bong-Kiun Kaang (๊ฐ๋ด๊ท ), C. Justin Lee (์ด์ฐฝ์ค) & Wuhyun Koh (๊ณ ์ฐํ).ย Nature Communications
DOI:10.1038/s41467-026-75009-5
Abstract
Astrocytic Ankyrin-2 Enables Memory Persistence in the Mouse Hippocampus
Memory persistence, the ability to retain information over time, is a fundamental feature of long-term memory. Although astrocytes contribute to synaptic plasticity, the molecular mechanisms by which they support memory persistence remain unclear.
Here we show that astrocytic ankyrin-2 (Ank2) is required for memory persistence in adult mice. Astrocyte-specific deletion of Ank2 impaired remote memory without affecting recent memory and disrupted the maintenance of long-term potentiation.
Loss of Ank2 reduced astrocyte contacts with engram neurons and impaired astrocyte morphogenesis driven by brain-derived neurotrophic factor (BDNF) signaling through the truncated tropomyosin receptor kinase B receptor (TrkB.T1) and inositol 1,4,5-trisphosphate receptor type 2 (IP3R2). Consistent with this mechanism, astrocytic Ank2 was required for the enhancement of memory persistence by hippocampal BDNF infusion.
Furthermore, selective optogenetic activation of astrocytic TrkB.T1 signaling enhanced remote memory, demonstrating that astrocytic BDNF signaling is sufficient to promote memory persistence. These findings identify astrocytic Ank2 as a key regulator of long-term memory persistence.
