Optogenetics has been widely expanded to enhance or suppress neuronal activity and it has been recently applied to glial cells. Here, we have used a new approach based on selective expression of melanopsin, a G‐protein‐coupled photopigment, in astrocytes to trigger Ca2+ signaling. Using the genetically encoded Ca2+ indicator GCaMP6f and two‐photon imaging, we show that melanopsin is both competent to stimulate robust IP3‐dependent Ca2+ signals in astrocyte fine processes, and to evoke an ATP/Adenosine‐dependent transient boost of hippocampal excitatory synaptic transmission. Additionally, under low‐frequency light stimulation conditions, melanopsin‐transfected astrocytes can trigger long‐term synaptic changes. In vivo, melanopsin‐astrocyte activation enhances episodic‐like memory, suggesting melanopsin as an optical tool that could recapitulate the wide range of regulatory actions of astrocytes on neuronal networks in behaving animals. These results describe a novel approach using melanopsin as a precise trigger for astrocytes that mimics their endogenous G‐protein signaling pathways, and present melanopsin as a valuable optical tool for neuron–glia studies.
