title: The inhibitory input to mouse cerebellar Purkinje cells is reciprocally modulated by Bergmann glial P2Y1 and AMPA receptor signaling.
abstract: Synaptic transmission has been shown to be modulated by glial functions, but the modes of specific glial action may vary in different neural circuits. We have tested the hypothesis, if Bergmann GLIA (BG) are involved in shaping neuronal communication in the mouse cerebellar cortex, using acutely isolated cerebellar slices of wild-type (WT) and of glia-specific receptor knockout mice. Activation of P2Y1 receptors by ADP (100 µM) or glutamatergic receptors by AMPA (0.3 µM) resulted in a robust, reversible and repeatable rise of evoked inhibitory input in Purkinje cells by 80% and 150%, respectively. The ADP-induced response was suppressed by prior application of AMPA, and the AMPA-induced response was suppressed by prior application of ADP. Genetic deletion or pharmacological blockade of either receptor restored the response to the other receptor agonist. Both ADP and AMPA responses were sensitive to Rose Bengal, which blocks vesicular glutamate uptake, and to the NMDA receptor antagonist D-AP5. Our results provide strong evidence that activation of both ADP and AMPA receptors, located on BGs, results in the release of glutamate, which in turn activates inhibitory interneurons via NMDA-type glutamate receptors. This infers that BG cells, by means of metabotropic signaling via their AMPA and P2Y1 receptors, which mutually suppress each other, would interdependently contribute to the fine-tuning of Purkinje cell activity in the cerebellar cortex. GLIA 2016. GLIA 2016;64:1265-1280.
authors.affiliation: General Zoology, FB Biology, University of Kaiserslautern, P.B. 3049, D-67653, Kaiserslautern, Germany.
authors.forename: Ramona
authors.initials: R
authors.lastname: Rudolph
authors.affiliation: Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, D-66421 Homburg/Saar, Germany.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jahn
authors.affiliation: General Zoology, FB Biology, University of Kaiserslautern, P.B. 3049, D-67653, Kaiserslautern, Germany.|Weill Cornell Medical College, Doha, Qatar.
authors.forename: Raphael
authors.initials: R
authors.lastname: Courjaret
authors.affiliation: General Zoology, FB Biology, University of Kaiserslautern, P.B. 3049, D-67653, Kaiserslautern, Germany.
authors.forename: Nanette
authors.initials: N
authors.lastname: Messemer
authors.affiliation: Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, D-66421 Homburg/Saar, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: General Zoology, FB Biology, University of Kaiserslautern, P.B. 3049, D-67653, Kaiserslautern, Germany.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D027341:Excitatory Amino Acid Transporter 1; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; C546383:P2ry1 protein, mouse; D018091:Receptors, AMPA; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000255:Adenosine Triphosphate
keywords: ADP; NMDA receptors; gliotransmission; glutamate