Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices

Cristina Bertollini; Davide Ragozzino; Cornelius Gross; Cristina Limatola; Fabrizio Eusebi

doi:10.1016/j.neuropharm.2006.05.027

Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices

Neuropharmacology. 2006 Sep;51(4):816-21. doi: 10.1016/j.neuropharm.2006.05.027. Epub 2006 Jul 11.

Authors

Cristina Bertollini¹, Davide Ragozzino, Cornelius Gross, Cristina Limatola, Fabrizio Eusebi

Affiliation

¹ Istituto Pasteur-Fondazione Cenci Bolognetti & Dipartimento di Fisiologia Umana e Farmacologia, Università La Sapienza, Centro di Eccellenza BEMM, 00185 Roma, Italy.

PMID: 16815480
DOI: 10.1016/j.neuropharm.2006.05.027

Abstract

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 nH 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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
CX3C Chemokine Receptor 1
Chemokine CX3CL1
Chemokines, CX3C / immunology
Chemokines, CX3C / pharmacology
Dose-Response Relationship, Drug
Electric Stimulation / methods
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / physiology*
Excitatory Postsynaptic Potentials / radiation effects
Hippocampus / cytology
Hippocampus / drug effects
Hippocampus / physiology*
Humans
In Vitro Techniques
Membrane Proteins / immunology
Membrane Proteins / pharmacology
Mice
Mice, Knockout
Neural Inhibition / drug effects
Neural Inhibition / physiology
Neural Inhibition / radiation effects
Patch-Clamp Techniques / methods
Receptors, Chemokine / deficiency
Receptors, Chemokine / physiology*
Synaptic Transmission / drug effects
Synaptic Transmission / physiology*
Synaptic Transmission / radiation effects

Substances

CX3C Chemokine Receptor 1
CX3CL1 protein, human
Chemokine CX3CL1
Chemokines, CX3C
Cx3cl1 protein, mouse
Cx3cr1 protein, mouse
Membrane Proteins
Receptors, Chemokine