This paper details research on how astrocytes interact with multiple synapses through specialized leaflet domains. Using advanced imaging techniques like Focused Ion Beam/Scanning Electron Microscopy (FIB-SEM) and two-photon calcium imaging, the authors structurally define astrocyte leaflets as thin processes characterized by a high surface-to-volume ratio, the exclusion of mitochondria, and the presence of tiny intraluminal endoplasmic reticulum (i-ER) saccules. Crucially, the study refines the "tripartite synapse" concept by showing that most synapses are embedded in "tripartite synaptic networks," where connected leaflet domains (via gap junctions) integrate signals from multiple synapses. Furthermore, the researchers demonstrate that local calcium elevations in these leaflet domains are synaptic activity-dependent and triggered by IP$_3$R1 receptors expressed on the i-ER, distinguishing this signaling from activity associated with mitochondria.

References:

• Benoit, Lucas, et al. "Astrocytes functionally integrate multiple synapses via specialized leaflet domains." Cell (2025).