CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity

Justin T. Rogers, Josh M. Morganti, Adam D. Bachstetter, Charles E. Hudson, Melinda M. Peters, Bethany A. Grimmig, Edwin J. Weeber, Paula C. Bickford, Carmelina Gemma

Research output: Contribution to journalArticlepeer-review

462 Scopus citations


The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on theCNSinsult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions. No approach to date has been taken to decipher the significance of defects in CX3CL1/CX3CR1 signaling in physiological condition. In the present study we used CX3CR -/-, CX3CR1 +/-, and wild-type mice to investigate the physiological role of CX3CR1 receptor in cognition and synaptic plasticity. Our results demonstrate for the first time that mice lacking the CX3CR1 receptor show contextual fear conditioning and Morris water maze deficits. CX3CR1 deficiency also affects motor learning. Importantly, mice lacking the receptor have a significant impairment in long-term potentiation (LTP). Infusion with IL-1β receptor antagonist significantly reversed the deficit in cognitive functionandimpairment in LTP.Ourresults reveal that under physiological conditions, disruption in CX3CL1 signaling will lead to impairment in cognitive function and synaptic plasticity via increased action of IL-1β.

Original languageEnglish
Pages (from-to)16241-16250
Number of pages10
JournalJournal of Neuroscience
Issue number45
StatePublished - Nov 9 2011

ASJC Scopus subject areas

  • Neuroscience (all)


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