Visual input drives diverse ER calcium signals in neurons in vivo

The endoplasmic reticulum (ER) has long been thought to shape calcium signals in neurons, but stimulus-driven ER calcium fluctuations have not been directly measured in vivo. To measure neuronal ER calcium signals in vivo, we paired visual stimulus presentation with two photon imaging of ER and cytosolic calcium reporters in four different cell types in the Drosophila visual system. We found that visual input elicits diverse ER calcium signals, with the ER acting as a calcium sink or source depending on the cell type, subcellular compartment (dendrite versus axon), and type of visual stimulus. ER calcium signals were not simply a reflection of cytosolic signals, indicating that the ER, rather than acting as a passive calcium buffer, actively processes calcium signals in neurons in a context-specific fashion. Thus, ER-based signal processing may contribute to functional diversity across neuronal cell types, thereby enhancing the computational capacity of neural circuits.