Recent research published in Nature by scientists from Baylor College of Medicine is reshaping our understanding of memory. Previously, it was believed that memory functions were solely linked to the activities of neurons—brain cells that respond to learning experiences and assist in recalling memories. However, the Baylor team has broadened this perspective by demonstrating that non-neuronal cells known as astrocytes—star-shaped brain cells—play a significant role in memory storage and collaborate with groups of neurons called engrams to manage memory retention and retrieval.
Dr. Benjamin Deneen, a professor and the principal investigator at Baylor, noted, “The traditional view has been that only neuronal engrams are involved in forming and recalling memories, which respond to specific experiences.”
He added, “Our laboratory has a rich history of exploring astrocytes and their interactions with neurons. We discovered that these cells are closely linked both physically and functionally, which is crucial for brain operation. However, the specific function of astrocytes in memory storage and retrieval had not been examined previously.”
Astrocytes and Memory Recall
The research team initiated their work by creating innovative laboratory tools to observe the activity of astrocytes involved in memory-related brain circuits.
In typical experiments, the mice were conditioned to experience fear in a particular scenario and would ‘freeze’ in response. When these mice were later placed back in that same scenario, they would freeze due to their memory. Conversely, if they were in a different environment, they would not freeze as it was outside the context in which they were trained to fear.
Co-first author Dr. Wookbong Kwon, a postdoctoral associate in Deneen’s lab, stated, “Using our newly developed laboratory tools with these mice helped us confirm that astrocytes significantly contribute to recalling memories.”
The study found that during experiences like fear conditioning, certain astrocytes in the brain activate a gene called c-Fos. These astrocytes then regulate the functioning of neural circuits in that region of the brain.
Dr. Michael R. Williamson, another co-first author, explained, “Astrocytes expressing c-Fos are closely located to engram neurons. We observed that these engram neurons and the neighboring astrocyte group are also functionally linked. Activating the astrocyte group enhances synaptic activity in the associated neuron engram, indicating a bidirectional communication between astrocytes and neurons.”
In non-fearful situations, the mice did not freeze. “However, after activating the astrocyte group while they were in a safe environment, the mice still froze, suggesting that astrocyte activation can trigger memory recall,” Kwon remarked.
To dive deeper into the mechanisms behind the activity of astrocyte groups in memory recall, the researchers examined the gene NFIA. “We have previously found that astrocytic NFIA influences memory circuits, but its role within astrocyte groups in coordinating memory storage and recall was unclear,” Williamson noted.
The team observed that astrocytes that were activated by learning experiences had increased levels of the NFIA protein. Blocking NFIA production in these astrocytes hindered memory recall, and strikingly, this suppression was specific to particular memories.
“By removing the NFIA gene in astrocytes that were active during learning, we disabled the animals’ ability to recall that specific memory while they still remembered others,” Kwon said.
Dr. Deneen concluded, “These findings clarify the role astrocytes play in memory. The groups of astrocytes involved in one learning event are distinct from those that manage different memories. Likewise, the associated neuron groups differ as well.”
This research offers a more comprehensive view of the various elements and processes at play in the brain during the formation and recall of memories. Additionally, it provides fresh insights that may be significant for understanding human conditions related to memory loss, such as Alzheimer’s disease, and disorders characterized by reoccurring, hard-to-suppress memories, like post-traumatic stress disorder.
Other contributors to this research include Junsung Woo, Yeunjung Ko, Ehson Maleki, Kwanha Yu, Sanjana Murali, and Debosmita Sardar, all from Baylor College of Medicine.
This research received funding from multiple U.S. National Institutes of Health grants (R35-NS132230, R21-MH134002, and R01-AG071687), grant AHA-23POST1019413, and support from the National Research Foundation of Korea (RS-2024-00405396). Extra assistance was provided by the David and Eula Wintermann Foundation and the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development through award P50HD103555.
