Thrilled to share this work from my postdoc with Tom Carmichael, available online @ Neuron! Long story short: we find even more evidence that all reactive astrocytes are not equal, and we can take advantage of those differences to improve repair after stroke.
www.sciencedirect.com/science/arti...

Many thanks Ciaran!

Landmark publication from @junnagai.bsky.social lab!

Incredible work really detailing the neural mechanisms that recruit astrocyte ensembles ! 🤩
www.nature.com/articles/s41...

In sum, the astrocyte ensemble provides a slow, multiday dimension to memory processing, complementing fast neuronal activity. They may ensure that only selected experiences become stable memories. 8/8
Read the full paper: nature.com/articles/s41... Tools: addgene.org/Jun_Nagai/

Concept: Astrocytic ensembles act as multiday traces that integrate emotional state and memory information across days. They bridge discrete experiences (conditioning and recall) for stabilization and may explain why spaced learning is more effective than massed learning. 7/8

Function: Inhibiting these recall-astrocytic ensembles using a new silencing tool (iβARK2) destabilized memories. Conversely, reinforcing the astrocyte ensembles over-stabilized and generalized memories. The astrocyte ensemble thus determines memory stability and precision. 6/8

To our surprise, conditioning induced slow, multiday transcriptional changes in astrocytes, including upregulation of adrenoceptors (multiday primed state). Upon recall, coincident noradrenaline release and local engram activity triggered astrocytic Fos and Igfbp2 expression for their functions. 5/8

First finding: Astrocytic ensembles were sparse during the initial fear experience but widely recruited during memory recall a day later. These ensembles appeared in regions containing neuronal engrams, suggesting a delayed, experience-dependent trace left in some astrocytes. 4/8

Approach: We developed a brain-wide astrocyte Fos-tagging and imaging system combining AAV-PHP.eB vectors, Fos-iCreERT2 TRAP2 mice, and serial two-photon tomography. This enables single-cell level, whole brain mapping of behaviorally-relevant astrocyte ensembles in mice. 3/8

Not all experiences become stable memories. Emotionally salient or repeated experiences are often stabilized, but the mechanism has remained elusive. We asked whether astrocytes, rather than neurons, might provide the missing cellular substrate for this stabilization process. 2/8

Just out in Nature! “The astrocytic ensemble acts as a multiday trace to stabilize memory.” We identified astrocytic ensembles that link experiences across days to stabilize memory nature.com/articles/s41.... New astrocyte tools are openly available at Addgene: addgene.org/Jun_Nagai/. 1/8