LTP impairment by fractalkine/CX₃CL1 in mouse hippocampus is mediated through the activity of adenosine receptor type 3 (A₃R)

Abstract 

We have examined how the chemokine fractalkine/CX₃CL1 influences long-term potentiation (LTP) in CA1 mouse hippocampal slices. Field potentials (fEPSPs) were recorded upon electrical stimulation of Schaffer collaterals. It was found that application of CX₃CL1 inhibits LTP when present during the critical induction period. LTP impairment (i) failed to occur in CX₃CR1 deficient mice (CX₃CR1^GFP/GFP) and in the presence of okadaic acid (OA); (ii) required the activation of adenosine receptor 3 (A₃R), since it was prevented in A₃R-deficient mice or by MRS1523, a selective A₃R antagonist. Together, these findings indicate that CX₃CL1 inhibits hippocampal LTP through A₃R activity.

Abbreviations: LTP, long-term potentiation, LTD, long-term depression, fEPSPs, field evoked post-synaptic potentials, CNS, central nervous system, mice CX₃CR1^GFP/GFP, mice lacking CX₃CR1, A₁R, adenosine A₁ receptor, A_2AR, adenosine A_2A receptor, A_2BR, adenosine A_2B receptor, A₃R, adenosine A₃ receptor 3, HEK cells, human embryonic kidney 293 cells, PP, protein phosphatase, OA, okadaic acid, AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, MRS1523, 3-propyl-6-ethyl-5-[(ethylthio) carbonyl]-2phenyl-4-propyl-3-pyridine carboxylate, SCH58261, 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, CGS15943, 9-Chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine, ACSF, artificial cerebrospinal fluid, DPCPX, 8-Cyclopentyl-1,3-dipropylxanthine, FSK, forskolin

Keywords: Chemokine, LTP, Hippocampus, Glutamate receptor, fEPSP, Adenosine receptor