Dopamine is a key neurotransmitter involved in physiological processes, such as learning and memory, motor control and reward, as well as, pathological conditions, such as Parkinson's disease and drug abuse. In contrast to the extensive studies on neurons, the role of astrocytes 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 that is enhanced by amphetamine, a psychostimulant drug that acts via increasing dopamine levels. In brain slices, synaptically-released dopamine increases astrocyte Ca2+ and stimulates the release of ATP/adenosine, which leads to excitatory synaptic depression through activation of presynaptic adenosine A1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent activation of presynaptic A1 receptors. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the synaptic regulation induced by dopamine and amphetamine, revealing a novel cellular pathway in the brain reward system.

Major hallmarks of astrocyte physiology are the elevation of intracellular calcium in response to neurotransmitters and the release of neuroactive substances (gliotransmitters) that modulate neuronal activity. While μ-opioid receptor expression has been identified in astrocytes of the nucleus accumbens, the functional consequences on astrocyte–neuron communication remains largely unknown. The present study has investigated the astrocyte responsiveness to μ-opioid signaling and the regulation of gliotransmission in the nucleus accumbens. Through the combination of calcium imaging and whole-cell patch clamp electrophysiology in brain slices, we have found that μ-opioid receptor activation in astrocytes elevates astrocyte cytoplasmic calcium and stimulates the release of the gliotransmitter glutamate, which evokes slow inward currents through the activation of neuronal N-methyl-D-aspartate (NMDA) receptors. These results indicate the existence of molecular mechanisms underlying opioid-mediated astrocyte–neuron signaling in the nucleus accumbens.

No abstract

No abstract

No abstract