title: Dopamine elevates and lowers astroglial Ca2+through distinct pathways depending on local synaptic circuitry.
abstract: Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca2+rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca2+in cells connected via gap junctions to astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca2+] measurements, we also employed life-time imaging of the Ca2+indicator Oregon Green BAPTA-1. We found that dopamine triggered a dose-dependent, bidirectional Ca2+response in stratum radiatum astroglia, a jagged elevation accompanied and followed by below-baseline decreases. The elevation depended on D1/D2 receptors and engaged intracellular Ca2+storage and removal whereas the dopamine-induced [Ca2+] decrease involved D2 receptors only and was sensitive to Ca2+channel blockade. In contrast, the stratum lacunosum moleculare astroglia generated higher-threshold dopamine-induced Ca2+responses which did not depend on dopamine receptors and were uncoupled from the prominent inhibitory action of dopamine on local perforant path synapses. Our findings thus suggest that a single neurotransmitter-dopamine-could either elevate or decrease astrocyte [Ca2+] depending on the receptors involved, that such actions are specific to the regional neural circuitry and that they may be causally uncoupled from dopamine actions on local synapses. The results also indicate that [Ca2+] elevations commonly detected in astroglia can represent the variety of distinct mechanisms acting on the microscopic scale. GLIA 2017;65:447-459.
authors.affiliation: UCL Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Alistair
authors.initials: A
authors.lastname: Jennings
authors.affiliation: UCL Institute of Neurology, University College London, London, United Kingdom.|Institute of Neuroscience, University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Tyurikova
authors.affiliation: UCL Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Lucie
authors.initials: L
authors.lastname: Bard
authors.affiliation: UCL Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Institute of Neuroscience, University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.|RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Alexey
authors.initials: A
authors.lastname: Semyanov
authors.affiliation: UCL Institute of Neurology, University College London, London, United Kingdom.|Institute of Cellular Neurosciences, University of Bonn Medical School, Germany.|German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Henneberger
authors.affiliation: UCL Institute of Neurology, University College London, London, United Kingdom.|Institute of Neuroscience, University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Rusakov
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D061848:Optical Imaging; D018408:Patch-Clamp Techniques; D051381:Rats; D013569:Synapses / Q000187:drug effects*
chemical_list: D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D002118:Calcium; D004298:Dopamine
keywords: astroglia; calcium; dopamine; hippocampus; synaptic transmission