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Neuron. 2017 Jul 19;95(2):341-356.e6. doi: 10.1016/j.neuron.2017.06.020. Epub 2017 Jul 6.

Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia.

Author information

1
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: lindsay.debiase@nih.gov.
2
Intramural Research Program, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
3
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
4
Division of Rheumatology, Bayview Flow Cytometry Core, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
5
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: antonello.bonci@nih.gov.

Abstract

Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei. Region-specific phenotypes of BG microglia emerged during the second postnatal week and were re-established following genetic or pharmacological microglial ablation and repopulation in the adult, indicating that local cues play an ongoing role in shaping microglial diversity. These findings demonstrate that microglia in the healthy brain exhibit a spectrum of distinct functional states and provide a critical foundation for defining microglial contributions to BG circuit function.

KEYWORDS:

RNA sequencing; density; development; electrophysiology; heterogeneity; microglia; morphology; nucleus accumbens; substantia nigra; ventral tegmental area

PMID:
28689984
PMCID:
PMC5754189
DOI:
10.1016/j.neuron.2017.06.020
[Indexed for MEDLINE]
Free PMC Article

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