A novel mechanism is described through which activity acts on the neurovascular unit to promote synaptic transmission.

View all comments by Ben Barres

One of the salient outcomes that could reshape our thinking about the role of astrocytes in AD is that calcium signaling alterations linked to dense-core plaque deposits extend beyond the spatial domain of the discrete histopathology, and can synchronize larger populations of astrocyte and astrocyte circuits, either through extracellular signaling or gap junctions. What that calcium is doing, its originating source, and how it affects neurophysiology has yet to be determined in these models.

Certainly, a strength of this study is the confirmation of cell type, as previous in-vivo studies have not done so with certainty and were claiming changes in neuronal calcium signaling, and may have largely been observing astrocytes or other cell types. A potential overinterpretation in this study is relying only on methoxy-X04 staining as an indicator of plaque presence, as this only stains insoluble, late-stage, dense-core deposits and not other perhaps more pathogenic forms such as oligomers and other soluble β amyloid species. In addition, it would be quite interesting to compare...  Read more

One of the salient outcomes that could reshape our thinking about the role of astrocytes in AD is that calcium signaling alterations linked to dense-core plaque deposits extend beyond the spatial domain of the discrete histopathology, and can synchronize larger populations of astrocyte and astrocyte circuits, either through extracellular signaling or gap junctions. What that calcium is doing, its originating source, and how it affects neurophysiology has yet to be determined in these models.

Certainly, a strength of this study is the confirmation of cell type, as previous in-vivo studies have not done so with certainty and were claiming changes in neuronal calcium signaling, and may have largely been observing astrocytes or other cell types. A potential overinterpretation in this study is relying only on methoxy-X04 staining as an indicator of plaque presence, as this only stains insoluble, late-stage, dense-core deposits and not other perhaps more pathogenic forms such as oligomers and other soluble β amyloid species. In addition, it would be quite interesting to compare calcium signaling differences between the APP and APP/PS1 mice.

View all comments by Grace (Beth) Stutzmann