Melanopsin for precise optogenetic activation of astrocyte-neuron networks

Sara Mederos; Alicia Hernández-Vivanco; Jorge Ramírez-Franco; Mario Martín-Fernández; Marta Navarrete; Aimei Yang; Edward S Boyden; Gertrudis Perea

doi:10.1002/glia.23580

Melanopsin for precise optogenetic activation of astrocyte-neuron networks

Glia. 2019 May;67(5):915-934. doi: 10.1002/glia.23580. Epub 2019 Jan 11.

Authors

Sara Mederos¹, Alicia Hernández-Vivanco¹, Jorge Ramírez-Franco¹, Mario Martín-Fernández², Marta Navarrete³, Aimei Yang⁴, Edward S Boyden^{4

5}, Gertrudis Perea¹

Affiliations

¹ Department of Functional and Systems Neurobiology, Instituto Cajal, CSIC, Madrid, Spain.
² Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota.
³ Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.
⁴ Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts.
⁵ McGovern Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts.

PMID: 30632636
DOI: 10.1002/glia.23580

Abstract

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.

Keywords: astrocytes; melanopsin; neuron-glia interactions; optogenetics; synaptic plasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

2-Amino-5-phosphonovalerate / pharmacology
Adenosine A2 Receptor Antagonists / pharmacology
Alanine / analogs & derivatives
Alanine / pharmacology
Animals
Astrocytes / metabolism*
Azo Compounds / pharmacology
Channelrhodopsins / genetics
Channelrhodopsins / metabolism
Chelating Agents / pharmacology
Egtazic Acid / analogs & derivatives
Egtazic Acid / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Glial Fibrillary Acidic Protein / genetics
Glial Fibrillary Acidic Protein / metabolism
Hippocampus / cytology
Inositol 1,4,5-Trisphosphate Receptors / genetics
Inositol 1,4,5-Trisphosphate Receptors / metabolism
Light
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Net / metabolism*
Neurons / metabolism*
Optogenetics / methods*
Pyridoxal Phosphate / analogs & derivatives
Pyridoxal Phosphate / pharmacology
Pyrimidines / pharmacology
Rod Opsins / genetics
Rod Opsins / metabolism*
Synaptic Potentials / physiology
Triazoles / pharmacology
Xanthenes / pharmacology

Substances

2-amino-2-(4-carboxyphenyl)-3-(9H-xanthen-9-yl)propanoic acid
5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
Adenosine A2 Receptor Antagonists
Azo Compounds
Channelrhodopsins
Chelating Agents
Excitatory Amino Acid Antagonists
Glial Fibrillary Acidic Protein
Inositol 1,4,5-Trisphosphate Receptors
Ip3r2 protein, mouse
MRS2159
Pyrimidines
Rod Opsins
Triazoles
Xanthenes
melanopsin
Egtazic Acid
Pyridoxal Phosphate
2-Amino-5-phosphonovalerate
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Alanine