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

Lindsay M. De Biase, Kornel Schuebel, Zachary H. Fusfeld, Kamwing Jair, Isobel A. Hawes, Raffaello Cimbro, Haiying Zhang, Qing Rong Liu, Hui Shen, Zheng Xiong Xi, David Goldman, Antonello Bonci

Research output: Contribution to journalArticle

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. De Biase et al. show that microglia in different basal ganglia nuclei exhibit region-specific phenotypes, with distinct anatomical features, lysosome content, membrane properties, and transcriptomes. Local regulatory cues guide establishment and maintenance of this regional specialization.

Original languageEnglish (US)
Pages (from-to)341-356.e6
JournalNeuron
Volume95
Issue number2
DOIs
Publication statusPublished - Jul 19 2017
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

De Biase, L. M., Schuebel, K., Fusfeld, Z. H., Jair, K., Hawes, I. A., Cimbro, R., ... Bonci, A. (2017). Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia. Neuron, 95(2), 341-356.e6. https://doi.org/10.1016/j.neuron.2017.06.020