How does the brain store and access our memories? Although our understanding of the brain has (thankfully) grown greatly since the days of taking brain tissue to see what would happen, a precise understanding of where our memories reside – and how our brain remembers past experiences – remains elusive.

A new paperpublished on November 6 in Natureexamines the role played by cells called astrocytes, named for their distinctive star-like shape, in how mice process and store their memories. The study suggests that these cells are involved in both the formation and storage of memories, and challenges the established theory that memories are only stored in our neurons.

Benjamin Deneen, the paper’s lead author, recounts Popular science that in the early days of neuroscience, research tended to focus on neurons, treating other cells as relatively unimportant supporting structures. However, as our understanding of the intricacies of the brain has grown, so has our appreciation that, while our neurons are certainly important, they are not the only cells that contribute to brain functionality. In particular, the role of non-neuronal cells called glial cells, of which astrocytes are an example, has been completely re-examined.

“(Astrocytes) have long been considered a monolithic support cell in the brain,” says Deneen. However, he continues, “our knowledge of astrocytes has undergone a renaissance over the past 20 years, highlighted by the identification of dynamic physiological activities, key roles in circuit function, and diverse molecular properties.”

The modern understanding is that astrocytes appear to be responsible for a wide variety of functions in the brain – so many, in fact, that it can be difficult to give a simple answer to the question of what they do. “My view is that astrocytes are sort of the ‘Swiss army knife’ of the brain,” says Deneen. “They interact with virtually every cell in the brain (and) a single astrocyte can contact up to 100,000 synapses.” He cites multiple examples of critical activities for which astrocytes are responsible: “(They) play an essential role in the formation of the blood-brain barrier; provide metabolic support to neurons, buffer ions and maintain ionic gradients; react to injury and degeneration; (and) interact with resident immune cells in the brain in response to injury or other insults.

However, despite their importance, we are only beginning to explore how astrocytes participate in the formation and storage of memories.

The prevailing understanding of how our brains store our memories is that a memory is distributed throughout the brain in a single network of neurons called an “engram.” As Deneen explains: “At the cellular level… each memory is made up of a different set of neurons distributed across a multitude of regions of the brain, i.e. an engram. It is important to note that a single neuron can participate in multiple engrams, but each engram is composed of a unique set of neurons.

The study examined how astrocytes in the brains of mice – and in particular a specialized variety known as “learning-associated astrocytes” or LAAs – acted during and after a learning experience. The researchers found that during such an experiment, some of these LAAs were activated; reactivation of the LAA in a different environment appears to stimulate memory recall and associated learning.

The researchers also found that LAAs activated by a learning experience maintained a high level of a protein expressed by a gene called NFIA. Preventing the production of this protein prevented the recall of the memory of the learning experience in question.

It therefore appears from this evidence that astrocytes play a role in both the storage and recall of memories. How does this fit with the generally accepted theory that memories are stored as engrams?

“That’s a question we’re wrestling with in the lab right now,” laughs Deneen. “One way to look at it goes back to the fact that astrocytes ‘listen’ to neurons and respond to meet the demands of a functional circuit. Under learning conditions, where a set of neurons has formed a memory engram, it is possible that neurons need to “offload” aspects of the memory to astrocytes, where the astrocyte serves as a safe or reservoir for the information stored by a given engram. neuron. »

Regardless, it is clear that there is still much to learn about the nuances of how memory works and that the apparent involvement of astrocytes raises many new questions and hints at many new possibilities. “It is clear that astrocytes are now involved in memory recall,” says Deneen. “It’s unclear whether they actually store memory or serve as a retrieval channel. Perhaps there is some “indexing” between astrocytes and neurons at the cellular level, where one neuron distributes its memory “information” to a multitude of nearby LAAs.

There are also many more questions to be answered about astrocytes themselves: for example, while LAAs are certainly specialized cells, it is not straightforward to know whether there are distinct, predetermined astrocyte types or a single cell that evolves to fulfill required roles. “I’ve spent over twenty years studying how astrocytes are made and what they do,” says Deneen, “and it’s not an easy question to answer…I think there are different subtypes of astrocytes, but this is not a simple question. blank question. There is evidence that different subtypes of astrocytes are encoded during development…but whether this “diversity” reflects a hard-wired, predetermined state or is an adaptation to their local environment…remains up for debate.