title: Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP.
abstract: To date, it has been difficult to reveal physiological Ca(2+) events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca(2+) signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca(2+) indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca(2+) signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca(2+) signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca(2+) transients by 30-40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca(2+) signals in processes and failed to affect the somatic Ca(2+) response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca(2+) signals that mimicked the stimulation-evoked astrocytic Ca(2+) responses. We conclude that stimulation-evoked Ca(2+) signals in astrocytic processes at CA3-CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP.
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, Department of Molecular Neurobiology and wannan.tang@medisin.uio.no e.a.nagelhus@medisin.uio.no.
authors.forename: Wannan
authors.initials: W
authors.lastname: Tang
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, Oslo University Hospital, Department of Neurology, 0027 Oslo, Norway.
authors.forename: Karolina
authors.initials: K
authors.lastname: Szokol
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Vidar
authors.initials: V
authors.lastname: Jensen
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, Oslo University Hospital, Department of Neurology, 0027 Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Enger
authors.affiliation: Neural Circuits and Behaviour Research Group, Department of Biomedical Optics, Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany, and.
authors.forename: Chintan A
authors.initials: CA
authors.lastname: Trivedi
authors.affiliation: Department of Physiology, and.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Hvalby
authors.affiliation: Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: P Johannes
authors.initials: PJ
authors.lastname: Helm
authors.affiliation: Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, and.
authors.forename: Loren L
authors.initials: LL
authors.lastname: Looger
authors.affiliation: Department of Molecular Neurobiology and.
authors.forename: Rolf
authors.identifier: http://orcid.org/0000-0003-3370-0970
authors.initials: R
authors.lastname: Sprengel
authors.affiliation: Centre for Molecular Medicine Norway, The Nordic EMBL Partnership, Letten Centre and GliaLab, Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, Oslo University Hospital, Department of Neurology, 0027 Oslo, Norway, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14618 wannan.tang@medisin.uio.no e.a.nagelhus@medisin.uio.no.
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D004148:Dioxolanes / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010648:Phenylacetates / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: C107349:2-chloro-5-hydroxyphenylglycine; D002147:Calmodulin; D004148:Dioxolanes; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D010648:Phenylacetates; D011687:Purines; D016704:Synapsins; C104068:4-(2-amino-6-chloro-9H-purin-9-yl)-1,3-dioxolane-2-methanol; D018698:Glutamic Acid; D008734:Methoxyhydroxyphenylglycol; D000255:Adenosine Triphosphate; D002118:Calcium; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol
keywords: GCaMP; astrocytes; endfeet; glia; hippocampus; two-photon