Scientists at the RIKEN Center for Brain Science in Japan have discovered that specialized brain cells known as astrocytes, previously thought to serve only supportive functions, actually play a critical role in stabilizing emotionally significant memories over several days. The study, published in Nature and titled “The astrocytic ensemble acts as a multiday trace to stabilize memory,” revealed that a specific group of astrocytes, termed the astrocytic ensemble, functions as a multiday molecular trace that preserves memories following emotionally charged experiences such as fear.
It is well established that neurons store memories in networks known as engrams. But this study demonstrates that astrocytes, which closely interact with neurons, also play a key role in memory stabilization. After an emotionally intense event, such as fear conditioning, certain astrocytes undergo gradual but long-lasting molecular and functional changes, becoming more responsive when the memory is later recalled.
To investigate this, researchers used a recently developed brain-wide Fos tagging technique to label astrocytes activated during certain behavioral events permanently. Mice were subjected to fear conditioning and recall tasks, and their brain activity was imaged across the whole brain. Interestingly, the activation of astrocytes was modest after the fear event, but increased dramatically during memory recall a day later, particularly in the amygdala, the brain’s emotional processing center. These active clusters, called fear recall astrocyte ensembles (FR-BAEs), were found to correlate with neighboring neuronal engrams, providing strong evidence that astrocytes cooperate with neurons to strengthen memory. Notably, this activation occurred during memory recall, not during the initial learning phase.
It was found that these groups of astrocytes were triggered by the combined action of noradrenaline, released by the locus coeruleus, and local neuronal transmission. To examine the action of noradrenaline, laboratory experiments revealed that noradrenaline acts as a beta-adrenergic receptor agonist, activating a cyclic AMP (cAMP) signaling pathway within astrocytes. Astrocyte activation was stronger when the signals of noradrenaline and glutamate occurred simultaneously. Blocking either noradrenaline signaling or local amygdala activity reduced the astrocytic responses, which confirmed that both inputs are necessary for activation.
After the fear conditioning, single-cell RNA-sequencing and imaging showed that over a period of one to three days, the receptor genes Adra1a and Adrb1 started being expressed more by the astrocytes. This functional molecular modification increased their sensitivity to noradrenaline during later recall. The molecular “priming” peaked one day following conditioning and diminished within two weeks, providing a temporary but critical window for memory stabilization.
The astrocyte ensembles were also found to contain high concentrations of IGFBP2, a protein known to influence synaptic plasticity and neural circuit remodeling. Blocking IGFBP2 during the memory recall impaired memory retention, whereas enhancing beta-adrenergic receptor signaling, which in turn increased IGFBP2 expression and strengthened memory stability. Nevertheless, excessive activation of this pathway resulted in generalization of fear, implying that too much activity of astrocytes can compromise memory precision.
This discovery redefines the role of astrocytes, showing that they are not merely support cells but active participants in the neural machinery of memory. By creating a multiday trace that integrates emotional and contextual information. Astrocyte ensembles help stabilize memories associated with repetitive or emotionally salient experiences so that memories that are related to survival are retained while maintaining flexibility in neural circuits.
These findings represent a major advance in neuroscience and indicate that the interaction between the astrocytes and the neurons plays an important role in the stabilization of long-term memory. Moreover, this insight opens promising avenues for developing treatments for memory-related disorders such as post-traumatic stress disorder (PTSD) and Alzheimer’s disease.
Reference: Dewa K, Kaseda K, Kuwahara A, et al. The astrocytic ensemble acts as a multiday trace to stabilize memory. Nature. 2025. doi:10.1038/s41586-025-09619-2
