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

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 t...

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Authors: Corkrum, Michelle, Covelo, Ana, Bellocchio, Luigi, Pisansky, Marc, Loke, Kelvin, Quintana, Ruth, Rothwell, Patrick E., Luján Miras, Rafael, Marsicano, Giovanni, Martín, Eduardo D., Thomas, Mark J., Kofuji, Paulo, Araque, Alfonso
Format: article
Publication Date:2020
Country:España
Institution:Universidad de Castilla-La Mancha
Repository:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/23800
Online Access:https://doi.org/10.1016/j.neuron.2019.12.026
http://hdl.handle.net/10578/23800
Access Level:Open access
Keyword:Astrocytes
Dopamine
Synaptic transmission
Amphetamine
Description
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.