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

Abstract	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 the CNS insult. 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 CX3CR1⁻/⁻, 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 function and impairment in LTP. Our results 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.
Authors	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
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 31 Issue 45 Pg. 16241-50 (Nov 09 2011) ISSN: 1529-2401 [Electronic] United States
PMID	22072675 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Aif1 protein, mouse Calcium-Binding Proteins Cytokines Interleukin 1 Receptor Antagonist Protein Microfilament Proteins Receptors, Interleukin-8A Bromodeoxyuridine
Topics	Analysis of Variance Animals Behavior, Animal (drug effects, physiology) Biophysics Bromodeoxyuridine (metabolism) Calcium-Binding Proteins (genetics, metabolism) Cerebellum (metabolism) Cognition Disorders (genetics, pathology) Conditioning, Psychological (physiology) Cytokines (metabolism) Disease Models, Animal Electric Stimulation Enzyme-Linked Immunosorbent Assay (methods) Excitatory Postsynaptic Potentials (drug effects, genetics) Exploratory Behavior (physiology) Fear (physiology) Gene Expression Regulation (genetics) Hippocampus (pathology, physiopathology) In Vitro Techniques Interleukin 1 Receptor Antagonist Protein (pharmacology) Long-Term Potentiation (genetics, physiology) Male Maze Learning (physiology) Mice Mice, Inbred C57BL Mice, Knockout Microfilament Proteins (genetics, metabolism) Microglia (pathology) Motor Activity (genetics) Neurogenesis (genetics) Patch-Clamp Techniques Receptors, Interleukin-8A (deficiency) Rotarod Performance Test

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