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Diversity of astrocyte functions and phenotypes in neural circuits

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Abstract

Astrocytes tile the entire CNS. They are vital for neural circuit function, but have traditionally been viewed as simple, homogenous cells that serve the same essential supportive roles everywhere. Here, we summarize breakthroughs that instead indicate that astrocytes represent a population of complex and functionally diverse cells. Physiological diversity of astrocytes is apparent between different brain circuits and microcircuits, and individual astrocytes display diverse signaling in subcellular compartments. With respect to injury and disease, astrocytes undergo diverse phenotypic changes that may be protective or causative with regard to pathology in a context-dependent manner. These new insights herald the concept that astrocytes represent a diverse population of genetically tractable cells that mediate neural circuit–specific roles in health and disease.

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Figure 1: Astrocytes are morphologically complex cells with numerous branches and branchlets in territories that are 60 μm in length along the longest axis.
Figure 2: Single astrocytes display diverse Ca2+ signals in territories.
Figure 3: Astrocytes in vivo respond with global Ca2+ elevations during electrical stimulation of the locus coeruleus (LC), during locomotion and during startle responses.
Figure 4: Diverse astrocyte functional responses to tissue injury and disease.

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Acknowledgements

B.S.K. is supported by the US National Institutes of Health (NIH; NS060677, MH099559A, MH104069) and the CHDI Foundation. M.V.S. is supported by NIH (NS084030), Wings for Life, Hilton Foundation, CHDI, and the Dr. Miriam and Sheldon B. Adelson Medical Research Foundation. The images shown in Figure 1 are from the The Cell Centered Database, which is supported by NIH grants from NCRR RR04050, RR RR08605, and the Human Brain Project DA016602 from the National Institute on Drug Abuse, the National Institute of Biomedical Imaging and Bioengineering, and the National Institute of Mental Health.

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Correspondence to Baljit S Khakh or Michael V Sofroniew.

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Khakh, B., Sofroniew, M. Diversity of astrocyte functions and phenotypes in neural circuits. Nat Neurosci 18, 942–952 (2015). https://doi.org/10.1038/nn.4043

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