Remembering a walk in the mountains, or a meal with the family. Each experience is encoded by a unique neural circuit that reactivates when we recall the memory. But in reality, neurons are not the only pieces of the puzzle. Other brain cells participate in the activation of these patterns: astrocytes. Researchers at Baylor College of Medicine (Texas, United States) have just revealed a new function of these cells in learning.
“ We discovered that astrocytes play a role in both memory encoding and recall," "summarizes Michael Williamson, author of the study, during an interview for Science and FutureTheir results were published in the prestigious journal Nature.
Memorization goes through three key stages
To remember a lesson, for example, the brain works in three phases. First, encoding allows the information to be processed in depth. During this stage, the brain captures and organizes the information so that it is understandable, which requires sustained attention. Then, during consolidation, the hippocampus, a brain structure, transforms the event into a lasting memory. Various repeated activities, such as quizzes, help to anchor the memory: the memory must be put to the test. Finally, the last phase, that of retrieval, consists of actively recalling the knowledge. The more regular the reminders, the more they promote long-term memory.
These memory processes leave physical and chemical traces in the brain. We speak of engrams. It is the physical manifestation of memory, simplifies the researcher. This idea was developed by Richard Semon in the 20th century, and strong evidence for its existence has been revealed over the last 15 years." Until now, it was thought that neurons were the only cells that produced these memory markers. But Michael Williamson's study reveals that astrocytes are also an active component of the engram.
What is an astrocyte?
But speaking of astrocytes, what exactly are they? These star-shaped cells populate the brain, and therefore live alongside neurons and other so-called "glial" cells, such as astrocytes, whose role is to support neurons. Astrocytes thus perform crucial functions for neuronal activity: they provide them with the necessary nutrients and regulate their chemical environment. According to the results of researchers from Baylor College of Medicine, astrocytes even play the role of mediator in the storage and retrieval of memories. They could influence the neuronal circuits that encode and recall our experiences.
But how? Each event activates a specific group of astrocytes, " about 3% of all astrocytes in the hippocampus, a brain structure essential for memory,” specifies Michael Williamson. “ We believe that each memory is represented by a distinct set of astrocytes that collectively regulate the consolidation and recall of that particular memory." A given astrocyte would therefore be responsible for storing several memories, each memory being distributed across a unique set of astrocytes (and neurons).
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Astrocytes reactivate fear memory
To study the role of astrocytes in memory, the researchers set up an experimental protocol on mice, which they subjected to fear conditioning. They were exposed to a particular environment in which they learned to associate a stimulus with a frightening event. In this context of fear, the mice reacted by freezing, which allowed the researchers to clearly identify when they remembered the traumatic event.
Next, the researchers used complex genetic systems to identify and manipulate the sets of astrocytes associated with fear learning. To do this, they used the c-Fos gene. This gene is expressed in response to learning, in groups of astrocytes specific to each event. Using a tool (called DREADD), Michael Williamson's team was able to specifically reactivate the group of astrocytes associated with fear learning. "The set of astrocytes activated during learning is capable of reactivating neurons, thus activating circuits associated with memory.", says Michael Williamson.
Thus, the researchers were able to test the impact of astrocyte activation on the behavior of mice in different contexts. Result: simple reactivation of astrocytes revived the memory of fear in the mice, which froze instantly, without stimulus. Astrocytes therefore do not just support neurons, but interact physically and functionally with them to form and reactivate memories. They participate directly in synaptic communication in memory circuits and are able to activate or reactivate these circuits in a targeted manner.
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A breakthrough in Alzheimer's disease research
To this first conclusion, the researchers reveal a second fascinating result. Another gene, called NFIA, is highly expressed in astrocytes activated during learning. This gives rise to a high level of the protein of the same name. Even more surprising: inhibiting the expression of the NFIA gene completely erases the memory. Indeed, without the protein associated with this gene, the mice did not react to the stimulus: they did not remember the traumatic event.
These discoveries shed light on new mechanisms of the complex process of memory. They open new perspectives for better understanding the Alzheimer's disease for example, which causes memory loss, or the post-traumatic stress disorder, which leads to inappropriate recall of memories. Our results indicate that astrocytes play an essential role in these complex diseases, concludes the author. Targeting astrocytes could therefore be a useful therapeutic avenue.. »
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