Melanopsin for precise optogenetic activation of astrocyte-neuron networks

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.The authors thank Dr. J. Chen (UCSD, CA, USA) for providing IP3R2−/− mice; Dr. W. Buño, Dr. E. Martin and Dr. Araque for helpful comments; Dr. JA Esteban, C. Sánchez and M.A. Muñoz for helpful assistance with the two‐photon technical assistance; Dr. M. Valero for MATLAB advice. This work was supported by PhD fellowship program (MINECO, BES‐2014‐067594) to S.M; and MINECO grants (BFU2013‐47265R; Intramural 201620I017; BFU2016‐75107‐P) to G.P