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 neurons—the 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.
“Our findings show that astrocytes are not passive support cells, but active regulators that determine how long memories last,” said Dr. KOH Wuhyun, corresponding author of the study. “By 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.”
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.
The study was published in Nature Communications on July 07, 2026.
Nature Communications
Experimental study
Animals
Astrocytic Ankyrin-2 Enables Memory Persistence in the Mouse Hippocampus
7-Jul-2026