Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices

This work reports the effect of chemokine fractalkine/CX₃CL1, an endogenous small peptide highly expressed in the central nervous system, on evoked synaptic responses investigated in mouse CA1 stratum radiatum using an electrophysiological approach. We report that in acute mouse hippocampal slices, superfusion of CX₃CL1 resulted in a reversible depression of the field excitatory postsynaptic potential (fEPSP) which developed within few seconds, increased for up to 10 min of application and disappeared within 30 min after the end of CX₃CL1 treatment. We also show that CX₃CL1-induced synaptic depression is (i) dose-dependent with IC₅₀ and n_H values of 0.7 nM and 1, respectively, (ii) not associated with a change in paired-pulse facilitation, (iii) mediated through CX₃CL1 receptor (CX₃CR1), being absent in CX₃CR1^-/- mice and inhibited in wild-type mice by a specific blocking antibody, and (iv) occluded by the induction of homosynaptic long-term depression (LTD). We conclude that CX₃CL1 is a potent neuromodulator of the evoked excitatory synaptic transmission, sharing common mechanisms with LTD.