On astrocyte-neuron interactions: Broad insights from the striatum

A long-standing question in biology and medicine concerns how astrocytes influence neurons. Here, progress concerning how astrocytes affect neurons and neural circuits is summarized by focusing on data and concepts from studies of the striatum, which has emerged as a model nucleus. Mechanisms broadly applicable across brain regions and disorders are emphasized, and knowledge gaps are described. Experiments spanning multiple scales of biology show that astrocytes regulate neural circuits by virtue of homeostatic signaling and through astrocyte-neuron interactions. During disease, astrocytes contribute to nervous system malfunction in context-specific ways through failures of normal functions and the development of maladaptive responses. As ideally positioned endogenous cellular neuromodulators, astrocytes can be targeted for strategies to regulate neural circuits in brain disorders. After a historically slow start for the field, astrocyte-neuron interactions are now recognized as consequential for physiology and behavior, critically involved in pathophysiology, and exploitable in disease.