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

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 (CX3CR1GFP/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.