In a groundbreaking study, scientists unveil a new dimension to memory storage and recall involving star-shaped brain cells called astrocytes. This discovery could significantly impact the study and treatment of memory-related conditions like Alzheimer’s and PTSD.
A groundbreaking study published in the journal Nature by researchers at Baylor College of Medicine and the Jan and Duncan Neurological Research Institute at Texas Children’s Hospital (Texas Children’s Duncan NRI) has unveiled a previously unknown player in the realm of memory storage and recall: astrocytes. These star-shaped, non-neuronal brain cells are now established as pivotal components in the orchestration of memory alongside neurons.
Traditionally, memory formation and retrieval have been attributed to the activity of neurons, specifically those forming engram cells — groups of neurons believed to store memories. However, this new research suggests that astrocytes also contribute significantly to these processes by working in concert with neuron engrams.
“The prevailing idea is that the formation and recall of memories only involves neuronal engrams that are activated by certain experiences, and hold and retrieve a memory,” corresponding author Benjamin Deneen, a professor in the Department of Neurosurgery at Baylor, said in a news release.
“Our lab has a long history of studying astrocytes and their interactions with neurons. We have found that these cells interact closely with each other, both physically and functionally, and that this is essential for proper brain function. However, the role of astrocytes in storage and retrieval of memories has not been investigated before,” he added.
Astrocytes Trigger Memory Recall
The research team began by creating advanced laboratory tools to understand the activity of astrocytes linked to memory circuits in the brain.
In their experiments, they conditioned mice to associate a certain context with fear. When returned to the same environment, the mice would ‘freeze’ due to fear recall. Interestingly, when the mice were in a different environment where they weren’t conditioned to feel fear, they did not freeze — unless specific astrocytes were activated.
“Working with these mice and with our new lab tools, we were able to show that astrocytes do play a role in memory recall,” co-first author Wookbong Kwon, a postdoctoral associate in the Deneen lab, said in the news release.
The key astrocytes in question express a gene known as c-Fos during learning events like fear conditioning. These c-Fos-expressing astrocytes were found to regulate the brain circuits involved in fear recall in a manner similar to their neighboring engram neurons.
“The c-Fos-expressing astrocytes are physically close with engram neurons,” added co-first author Michael R. Williamson, also a postdoctoral associate in the Deneen lab. “Furthermore, we found that engram neurons and the physically associated astrocyte ensemble also are functionally connected. Activating the astrocyte ensemble specifically stimulates synaptic activity or communication in the corresponding neuron engram. This astrocyte-neuron communication flows both ways; astrocytes and neurons depend on each other.”
Implications for Memory-Related Conditions
The researchers further explored the activity of the gene NFIA in astrocytes related to memory recall.
They discovered that astrocytes activated by learning experience elevated levels of NFIA protein, crucial for memory recall. Disabling NFIA production specifically impaired memory recall related to the conditioning event but did not affect other memories, underscoring the specificity of astrocyte involvement in individual memories.
“When we deleted the NFIA gene in astrocytes that were active during a learning event, the animals were not able to recall the specific memory associated with the learning event, but they could recall other memories,” Kwon added.
These findings challenge the long-held belief that only neurons are involved in memory recall and formation.
“Ensembles of learning-associated astrocytes are specific to that learning event. The astrocyte ensembles regulating the recall of the fearful experience are different from those involved in recalling a different learning experience,” said Deneen.
This paradigm shift opens new avenues for research into memory-related diseases, such as Alzheimer’s disease and conditions like post-traumatic stress disorder (PTSD), where memory recall plays a significant role. By understanding the dual involvement of neurons and astrocytes, researchers can develop more targeted treatments for these conditions.