Neuron
Volume 105, Issue 6, 18 March 2020, Pages 1036-1047.e5
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Article
Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity

https://doi.org/10.1016/j.neuron.2019.12.026Get rights and content
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Highlights

  • 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

Summary

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.

Keywords

astrocytes
dopamine
synaptic transmission
amphetamine
nucleus accumbens
calcium imaging
brain reward system

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