Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons

Davide Ragozzino, Silvia Di Angelantonio, Flavia Trettel, Cristina Bertollini, Laura Maggi, Cornelius Gross, Israel F. Charo, Cristina Limatola, Fabrizio Eusebi

Research output: Contribution to journalArticle

Abstract

We examined the effects of the chemokine fractalkine (CX3CL1) on EPSCs evoked by electrical stimulation of Schaffer collaterals in patch-clamped CA1 pyramidal neurons from rat hippocampal slices. Acute application of CX 3CL1 caused a sustained reduction of EPSC amplitude, with partial recovery after washout. CX3CL1-induced EPSC depression is postsynaptic in nature, because paired-pulse ratio was maintained, amplitude distribution of spontaneous excitatory postsynaptic currents shifted to lower values, and whole-cell current responses to AMPA were reversibly inhibited. EPSC depression by CX3CL1 is mediated by CX3CL1 receptor (CX3CR1), because CX3CL1 was unable to influence EPSC amplitude in CA1 pyramidal neurons from CX3CR1 knock-out mice. CX3CL1-induced depression of both EPSC and AMPA current was not observed in the absence of afferent fiber stimulation or AMPA receptor activation, respectively, indicating the requirement of sustained receptor activity for its development. Findings obtained from hippocampal slices, cultured hippocampal neurons, and transfected human embryonic kidney cells indicate that a Ca2+-, cAMP-, and phosphatase-dependent process is likely to modulate CX3CL1 effects because of the following: (1) CX3CL1-induced depression was antagonized by intracellular BAPTA, 8Br-cAMP, phosphatase inhibitors, and pertussis toxin (PTX); (2)CX 3CL1 inhibited forskolin-induced cAMP formation sensitive to PTX; and (3) CX3CL1 inhibited forskolin-induced Ser845 GluR1 phosphorylation, which was sensitive to PTX and dependent on Ca2+ and phosphatase activity. Together, these findings indicate that CX3CL1 negatively modulates AMPA receptor function at active glutamatergic synapses through cell-signaling pathways by influencing the balance between kinase and phosphatase activity.

Original languageEnglish
Pages (from-to)10488-10498
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number41
DOIs
Publication statusPublished - Oct 11 2006

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Keywords

  • Adenylate cyclase
  • AMPA receptors
  • Chemokines
  • EPSC depression
  • GluR1
  • Hippocampal slices
  • Phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ragozzino, D., Di Angelantonio, S., Trettel, F., Bertollini, C., Maggi, L., Gross, C., Charo, I. F., Limatola, C., & Eusebi, F. (2006). Chemokine fractalkine/CX3CL1 negatively modulates active glutamatergic synapses in rat hippocampal neurons. Journal of Neuroscience, 26(41), 10488-10498. https://doi.org/10.1523/JNEUROSCI.3192-06.2006