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Neuropsychopharmacology. 2019 Jan;44(2):344-355. doi: 10.1038/s41386-018-0151-4. Epub 2018 Jul 13.

Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling.

Author information

1
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. wxin2@jhmi.edu.
2
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. wxin2@jhmi.edu.
3
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, 20852, USA.
4
Department of Rheumatology, 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.
6
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. Antonello.bonci@nih.gov.
7
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Antonello.bonci@nih.gov.
8
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Antonello.bonci@nih.gov.
9
Department of Neuroscience, Georgetown University Medical Center, School of Medicine, Washington, DC, USA. Antonello.bonci@nih.gov.
10
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Antonello.bonci@nih.gov.

Abstract

Astrocytes are ubiquitous CNS cells that support tissue homeostasis through ion buffering, neurotransmitter recycling, and regulation of CNS vasculature. Yet, despite the essential functional roles they fill, very little is known about the physiology of astrocytes in the ventral midbrain, a region that houses dopamine-releasing neurons and is critical for reward learning and motivated behaviors. Here, using a combination of whole-transcriptome sequencing, histology, slice electrophysiology, and calcium imaging, we performed the first functional and molecular profiling of ventral midbrain astrocytes and observed numerous differences between these cells and their telencephalic counterparts, both in their gene expression profile and in their physiological properties. Ventral midbrain astrocytes have very low membrane resistance and inward-rectifying potassium channel-mediated current, and are extensively coupled to surrounding oligodendrocytes through gap junctions. They exhibit calcium responses to glutamate but are relatively insensitive to norepinephrine. In addition, their calcium activity can be dynamically modulated by dopamine D2 receptor signaling. Taken together, these data indicate that ventral midbrain astrocytes are physiologically distinct from astrocytes in cortex and hippocampus. This work provides new insights into the extent of functional astrocyte heterogeneity within the adult brain and establishes the foundation for examining the impact of regional astrocyte differences on dopamine neuron function and susceptibility to degeneration.

PMID:
30054584
PMCID:
PMC6300565
DOI:
10.1038/s41386-018-0151-4
[Indexed for MEDLINE]
Free PMC Article

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