Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling
PublisherNature Publishing Group
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AbstractAstrocytes 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. © 2018, The Author(s).
SponsorsThe authors would like to thank Dr. D.E. Bergles (Johns Hopkins University) for providing antibody to NG2, Dr. D.T. Lin (NIDA IRP) for assistance with two-photon imaging, and the NIDA IRP Transgenic breeding facility staff for assistance with animal husbandry. This research was supported by the NIDA and NIAAA Intramural Research Programs of the NIH, as well as an individual NSF grant to W.X. (grant no. 1232825). The Johns Hopkins Bayview Immunomics Core was supported by NIAMS (grant no. P30 AR-070254) for FACS services.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85050937258&doi=10.1038%2fs41386-018-0151-4&partnerID=40&md5=e508b4a8590c0cfd9b07eeca7df3e9ce; http://hdl.handle.net/10713/8623