When discussing memory, the academic world has long held that specific groups of neurons, known as engrams, are activated during learning and store memories, which are later recalled during relevant experiences.
A new study published in Nature reveals that another type of brain cell, astrocytes, form networks that regulate memory circuits in close collaboration with neurons.
The discovery, made by researchers at Baylor College of Medicine in Houston, reshapes our understanding of memory formation and potentially the treatment of memory-related disorders, like Alzheimer’s and post-traumatic stress disorder (PTSD), in which certain memories are repeatedly recalled and difficult to suppress.
Led by Benjamin Deneen, the scientists found that learning activates subsets of astrocytes in the hippocampus that regulate memory recall, indicating that these brain cells are also involved in the physical manifestation and expression of memories.
Astrocyte-Neuron Collaboration
Gertrudis Perea, who leads the neuro-glial networks lab at the Cajal Institute-CSIC, told SINC that this study is the first to show how astrocytes, in close collaboration with neurons, form networks that regulate memory circuits.
“Specifically, it describes the existence of groups of astrocytes that, like neurons, are activated during the process of conditioned fear in a specific environment, and how the activation of these astrocyte populations could trigger memory recall, even in different contexts,” explains Perea, who reviewed the study published in Nature.
Astrocytes are closely connected to neurons and play essential roles in regulating neuronal circuit function, including those associated with learning and memory. Additionally, they display experience-dependent plasticity, meaning their activation states, transcriptional responses, and functional properties align with environmental stimuli and internal states, according to the researchers.
This led Deneen’s group to hypothesize that astrocytes might actively participate in memory formation and retrieval in coordination with neuron assemblies.
To test this, they developed lab tools to identify astrocyte activity associated with memory-related brain circuits. They then conditioned mice to feel fear in a specific situation. Mice show fear by freezing, a behavior the researchers used as an indicator.
Regulation of Brain Circuits
The researchers demonstrated that during learning events, such as fear conditioning, a subset of astrocytes in the mice’s brains expressed a gene called c-Fos. They used this gene to verify if these astrocytes were involved in memorizing fear-inducing situations.
They specifically activated the subset of astrocytes expressing the c-Fos gene in mice that had experienced fear in a neutral setting. The animals froze even without a fear-inducing stimulus, showing that astrocyte activation was responsible for triggering the fear memory they had previously learned.
“These findings expand the notion that astrocytes exhibit experience-dependent plasticity, where their function adapts to sensory or social experiences, highlighting new roles in memory consolidation and recall,” the researchers explain.
“Traditionally, memory processes were thought to rely solely on neurons, specifically on groups called engrams. This study shows the existence of astrocyte subpopulations that directly participate in memory formation and retrieval,” notes Perea.
Deneen’s team identifies the nuclear factor I-A (NFIA) gene, which encodes a DNA-binding protein, as key to memory retrieval. This suggests that groups of astrocytes may be uniquely linked to particular memories, just like neurons, clarifies Perea.
Rising Importance of Astrocytes
Star-shaped (hence their name), astrocytes are the most abundant cell type in the brain, located close to neurons, and involved in processes that support neurotransmission and plasticity in brain circuits. However, they were long considered mere supportive or nourishing cells for neurons.
In 1998, Spanish researcher Alfonso Araque, then a postdoc in Philip Haydon’s lab in the U.S., proposed that astrocytes actively regulated synapses, a notion that was initially met with skepticism by the scientific community.
In 2007, Science recognized the “tripartite synapse” concept, in which astrocytes actively participate alongside neurons. The article acknowledged the findings from Gertrudis Perea’s Ph.D. work, which Araque supervised, and which she pursued after her postdoc stay in the U.S. before joining the Cajal Institute-CSIC.
Since then, astrocytes have been recognized for additional important functions, with the latest evidence being this new article. “This study highlights the potential of astrocytes to control processes that regulate memory formation, crucially influencing how we interact with the world, based on a continuous contrast between perception (external information) and memory (internal information),” concludes Perea. (Source: Agencia Sinc)
