title: Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex.
abstract: Accumulative evidence indicates that microglial cells influence the normal development of brain synapses. Yet, the mechanisms by which these immune cells target maturating synapses and influence their functional development at early postnatal stages remain poorly understood. Here, we analyzed the role of CX3CR1, a microglial receptor activated by the neuronal chemokine CX3CL1 (or fractalkine) which controls key functions of microglial cells. In the whisker-related barrel field of the mouse somatosensory cortex, we show that the recruitment of microglia to the sites where developing thalamocortical synapses are concentrated (i.e., the barrel centers) occurs only after postnatal day 5 and is controlled by the fractalkine/CX3CR1 signaling pathway. Indeed, at this developmental stage fractalkine is overexpressed within the barrels and CX3CR1 deficiency delays microglial cell recruitment into the barrel centers. Functional analysis of thalamocortical synapses shows that CX3CR1 deficiency also delays the functional maturation of postsynaptic glutamate receptors which normally occurs at these synapses between the first and second postnatal week. These results show that reciprocal interactions between neurons and microglial cells control the functional maturation of cortical synapses.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U603, 75006 Paris, France.
authors.forename: Maki
authors.initials: M
authors.lastname: Hoshiko
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnoux
authors.forename: Elena
authors.initials: E
authors.lastname: Avignone
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Etienne
authors.initials: E
authors.lastname: Audinat
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000378:metabolism; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013003:Somatosensory Cortex / Q000473:pathology*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000473:pathology*; D013788:Thalamus / Q000473:pathology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D019707:Receptors, Chemokine; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D049452:Green Fluorescent Proteins