Studies over the past two decades have demonstrated that astrocytes are tightly associated with neurons and play pivotal roles in neural circuit development, operation, and adaptation in health and disease. Nevertheless, precisely how astrocytes integrate diverse neuronal signals, modulate neural circuit structure and function at multiple temporal and spatial scales, and influence animal behavior or disease through aberrant excitation and molecular output remains unclear. This Perspective discusses how new and state-of-the-art approaches, including fluorescence indicators, opto- and chemogenetic actuators, genetic targeting tools, quantitative behavioral assays, and computational methods, might help resolve these longstanding questions. It also addresses complicating factors in interpreting astrocytes' role in neural circuit regulation and animal behavior, such as their heterogeneity, metabolism, and inter-glial communication. Research on these questions should provide a deeper mechanistic understanding of astrocyte-neuron assemblies' role in neural circuit function, complex behaviors, and disease.
Keywords: actuator; astrocytes; behavior; computational approaches; genetic targeting; indicator; neural circuit.
© 2022 The Authors. GLIA published by Wiley Periodicals LLC.