Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity
Neuron. 2020-03-01; 105(6): 1036-1047.e5
DOI: 10.1016/j.neuron.2019.12.026
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Corkrum M(1), Covelo A(2), Lines J(1), Bellocchio L(3), Pisansky M(1), Loke K(1), Quintana R(1), Rothwell PE(1), Lujan R(4), Marsicano G(3), Martin ED(5), Thomas MJ(1), Kofuji P(1), Araque A(6).
Author information:
(1)Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
(2)Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; INSERM, U1215 NeuroCentre Magendie, Bordeaux Cedex 33077, France; University of Bordeaux, Bordeaux 33000, France.
(3)INSERM, U1215 NeuroCentre Magendie, Bordeaux Cedex 33077, France; University of Bordeaux, Bordeaux 33000, France.
(4)Instituto de Investigación en Discapacidades Neurológicas (IDINE), Universidad Castilla-La Mancha, Albacete 02008, Spain.
(5)Instituto Cajal, CSIC, Madrid 28002, Spain.
(6)Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: .
Comment in
Neuron. 2020 Mar 18;105(6):954-956.
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.