CX3CL1-induced modulation at CA1 synapses reveals multiple mechanisms of EPSC modulation involving adenosine receptor subtypes.
We characterized the role of adenosine receptor (AR) subtypes in the modulation of glutamatergic neurotransmission by the chemokine fractalkine (CX3CL1) in mouse hippocampal CA1 neurons. CX(3)CL1 causes a reversible depression of excitatory postsynaptic current (EPSC), which is abolished by the A(3)R antagonist MRS1523, but not by A(1)R (DPCPX) or A(2A)R (SCH58261) antagonists. Consistently, CX3CL1-induced EPSC depression is absent in slices from A(3)R(-/-) but not A(1)R(-/-) or A(2A)R(-/-) mice. Further, A(3)R stimulation causes similar EPSC depression. In cultured neurons, CX3CL1-induced depression of AMPA current shows A(1)R-A(3)R pharmacology. We conclude that glutamatergic depression induced by released adenosine requires the stimulation of different ARs.
Piccinin
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S
Istituto Pasteur-Fondazione Cenci Bolognetti & Dipartimento di Fisiologia e Farmacologia Sapienza Università di Roma, Piazzale A. Moro 5, 00185 Rome, Italy.
Di Angelantonio
S
S
Piccioni
A
A
Volpini
R
R
Cristalli
G
G
Fredholm
B B
BB
Limatola
C
C
Eusebi
F
F
Ragozzino
D
D
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000235:genetics / Q000276:immunology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000276:immunology / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000502:physiology; D043684:Receptor, Adenosine A3 / Q000172:deficiency / Q000502:physiology; D043683:Receptors, Adenosine A2 / Q000172:deficiency / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000276:immunology*
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; D043682:Receptor, Adenosine A1; D043684:Receptor, Adenosine A3; D043683:Receptors, Adenosine A2; D018047:Receptors, Purinergic P1