Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson's disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A1 receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.
Bibliographical noteFunding Information:
We thank C. Nanclares, F.E. Labrada-Moncada, D. Deters, and S. Jamison for technical assistance and members of the Thomas lab and Araque lab for helpful suggestions. We thank E. Larson and the MnDRIVE Optogenetics Core at the University of Minnesota for academic and technical support and the acquisition of the fiber photometry system. We thank T. Nichols-Meade and M. Benneyworth at the Mouse Behavior Core, University of Minnesota and the personnel of the Animal Facility of NeuroCentre Magendie for academic and technical support. Work was done using a Leica SP5 multi-photon microscope at the University of Minnesota – University Imaging Centers. We thank the University of Minnesota Viral Vector and Cloning Core for production of some of the viral vectors used in this study. This work was supported by NIH-NIDA ( 1F30DA042510-01 ) to M.C., IdEx University of Bordeaux Investments for the Future program (France) to A.C., NIH-NINDS ( R01NS097312 ) and NIH-NIDA ( R01DA048822 ) to A.A., INSERM and European Research Council (MiCaBra, ERC-2017-AdG-786467 ) to G.M., Human Frontier Science Program (Research Grant RGP0036/2014 ) to A.A. and G.M., Salvador de Madariaga Program (Spain) to E.D.M., and ANR JCJC ( mitoCB1-fat ) to L.B.
© 2019 Elsevier Inc.
- brain reward system
- calcium imaging
- nucleus accumbens
- synaptic transmission
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural