Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity

• Published in: Neuron (Cambridge, Mass.) Mass.), 2020-03, Vol.105 (6), p.1036-1047.e5
• Main Authors: Corkrum, Michelle, Covelo, Ana, Lines, Justin, Bellocchio, Luigi, Pisansky, Marc, Loke, Kelvin, Quintana, Ruth, Rothwell, Patrick E., Lujan, Rafael, Marsicano, Giovanni, Martin, Eduardo D., Thomas, Mark J., Kofuji, Paulo, Araque, Alfonso
• Format: Article
• Language: English
• Subjects: Addictions; Adenosine; Adenosine - metabolism; Adenosine Triphosphate - metabolism; amphetamine; Amphetamine - pharmacology; Amphetamines; Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - physiology; brain reward system; Brain slice preparation; Calcium; Calcium - metabolism; calcium imaging; Clozapine - analogs & derivatives; Clozapine - pharmacology; Dopamine; Dopamine - physiology; Dopamine receptors; Excitatory Postsynaptic Potentials - physiology; Female; Genetics; Information processing; Male; Mice; Mice, Knockout; Mice, Transgenic; Motor Activity - physiology; Motor skill learning; Motor task performance; Movement disorders; Neurodegenerative diseases; Neurotransmission; Nucleus accumbens; Nucleus Accumbens - physiology; Optics; Optogenetics; Parkinson's disease; Pharmacogenetics; Receptor mechanisms; Receptors, Dopamine D1 - genetics; Reinforcement; Reward; Synaptic transmission; Synaptic Transmission - physiology; Transgenic mice
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2019.12.026

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. •Astrocytes in the Nucleus Accumbens respond to synaptic dopamine in vivo•Astrocytes mediate the synaptic regulation induced by dopamine and amphetamine•Amphetamine-induced enhancement in locomotion activity is modulated by astrocytes Corkrum et al. report that astrocyte activity is required for dopamine- and amphetamine-evoked synaptic regulation and amphetamine-induced locomotor effects. Their study reveals astrocytes as active components of dopaminergic signaling and the brain reward system.