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 language | English (US) |
|---|---|
| Pages (from-to) | 341-356.e6 |
| Journal | Neuron |
| Volume | 95 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 19 2017 |
| Externally published | Yes |
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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
Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia. / De Biase, Lindsay M.; Schuebel, Kornel; Fusfeld, Zachary H.; Jair, Kamwing; Hawes, Isobel A.; Cimbro, Raffaello; Zhang, Haiying; Liu, Qing Rong; Shen, Hui; Xi, Zheng Xiong; Goldman, David; Bonci, Antonello.
In: Neuron, Vol. 95, No. 2, 19.07.2017, p. 341-356.e6.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia
AU - De Biase, Lindsay M.
AU - Schuebel, Kornel
AU - Fusfeld, Zachary H.
AU - Jair, Kamwing
AU - Hawes, Isobel A.
AU - Cimbro, Raffaello
AU - Zhang, Haiying
AU - Liu, Qing Rong
AU - Shen, Hui
AU - Xi, Zheng Xiong
AU - Goldman, David
AU - Bonci, Antonello
PY - 2017/7/19
Y1 - 2017/7/19
N2 - 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.
AB - 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.
KW - density
KW - development
KW - electrophysiology
KW - heterogeneity
KW - microglia
KW - morphology
KW - nucleus accumbens
KW - RNA sequencing
KW - substantia nigra
KW - ventral tegmental area
UR - http://www.scopus.com/inward/record.url?scp=85021832099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021832099&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2017.06.020
DO - 10.1016/j.neuron.2017.06.020
M3 - Article
C2 - 28689984
AN - SCOPUS:85021832099
VL - 95
SP - 341-356.e6
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 2
ER -