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Deficiency of the Microglial Receptor CX3CR1 Impairs Postnatal Functional Development of Thalamocortical Synapses in the Barrel Cortex
Open accessAbstract
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.
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“KO mice lacking fractalkine receptor show transient excitatory hyperconnectivity followed by weak synaptic multiplicity and reduced functional brain connectivity in adulthood11,12, suggesting that a failure to eliminate synapses at the correct developmental time prevents the normal strengthening of synaptic connections.”
From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [12]
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Cites
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“…be that MGCs, once inside TCA clusters, could contribute to the selection of synapses with a mature signature of their glutamate receptors (Yashiro and Philpot, 2008) by pruning immature synapses through phagocytosis (Paolicelli et al., 2011) in a complement-dependent manner (Schafer et al., 2012).”
BackgroundMicroglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · cited 1×
“In the diseased adult CNS, several signaling pathways control the recruitment of microglia at sites of compromised homeostasis (Hanisch and Kettenmann, 2007; Ransohoff and Perry, 2009).”
BackgroundJung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · cited 3×
“In few experiments heterozygous CX3CR1 /eGFP mice of either sex were obtained by crossing CX3CR1 eGFP/eGFP (Jung et al., 2000) with wild-type C57BL/6J mice (Janvier).”
BackgroundMethodInfluentialNeurotrophins and their receptors: A convergence point for many signalling pathways
Chao, M. V. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1078 · Cited by 2,298
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · cited 1×
“In the diseased adult CNS, several signaling pathways control the recruitment of microglia at sites of compromised homeostasis (Hanisch and Kettenmann, 2007; Ransohoff and Perry, 2009).”
BackgroundControl of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · cited 1×
“This chemokine is expressed by neurons; its receptor CX3CR1 is only expressed by MGCs and controls their migration and functions (Harrison et al., 1998; Maciejewski-Lenoir et al., 1999; Cardona et al., 2006; Ruitenberg et al., 2008; Liang et al., 2009; Paolicelli et al., 2011).”
BackgroundControl of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344
Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10896 · Cited by 1,176 · cited 3×
“…local role of fractalkine in which cellular elements localized within the barrel hollows, possibly thalamic fibers, overexpress the chemokine at P5–P7 and thus favor directed migration of microglia (Harrison et al., 1998; Maciejewski-Lenoir et al., 1999) toward maturating thalamocortical synapses.”
BackgroundResultThe Role of Microglia in the Healthy Brain: Figure 1.
Tremblay, M.-È., Stevens, B., Sierra, A., Wake, H., Bessis, A., & Nimmerjahn, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4158-11.2011 · Cited by 992 · cited 1×
“In rodents, experimental evidence shows that MGCs contribute to developmentally regulated neuronal apoptosis but also to synapse pruning (Mallat et al., 2005; Pont-Lezica et al., 2011; Schlegelmilch et al., 2011; Tremblay et al., 2011).”
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Items 201–300 of 384
Integration of iPSC-Derived Microglia into Brain Organoids for Neurological Research
Mrza, M. A., He, J., & Wang, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063148 · Cited by 31
Oxytocin and microglia in the development of social behaviour
Gonzalez, A. M., & Hammock, E. A. D. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0059 · Cited by 32
“Microglia contribute to the process of synapse elimination [42,61,63,65,67], with impacts on social behaviour in adulthood [98].”
BackgroundDevelopment and sensory experience dependent regulation of microglia in barrel cortex
Kalambogias, J., Chen, C., Khan, S., Son, T., Wercberger, R., Headlam, C., Lin, C., & Brumberg, J. C. (2019) · The Journal of Comparative Neurology · doi:10.1002/cne.24771 · Cited by 32
“Although it has been shown that microglial processes play a pivotal role in the remodeling of dendritic spines in the visual system (Miyamoto et al., 2016; Tremblay & Majewska, 2011), their roles in the somatosensory barrel system has yet to be fully elucidated (Hoshiko et al., 2012).”
BackgroundInfluentialSynapse Dysfunctions in Multiple Sclerosis
Schwarz, K., & Schmitz, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021639 · Cited by 36
RORα Coordinates Thalamic and Cortical Maturation to Instruct Barrel Cortex Development
Vitalis, T., Dauphinot, L., Gressèns, P., Potier, M., Mariani, J., & Gaspar, P. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx262 · Cited by 28
Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human
Tewari, M., Michalski, S. A., & Egan, T. M. (2024) · Cells · doi:10.3390/cells13020161 · Cited by 36
“…the fractalkine/CX3CR1 receptor show a significant reduction in the number of microglia in the brain and a concurrent increase in the density of dendritic spines, suggesting that CX3CR1 guides the migration of the microglia responsible for pruning synapses in early development [123,124,135].”
BackgroundMicroglia‐leucocyte axis in cerebral ischaemia and inflammation in the developing brain
Rayasam, A., Fukuzaki, Y., & Vexler, Z. S. (2021) · Acta Physiologica · doi:10.1111/apha.13674 · Cited by 32
Microglial cells: Sensors for neuronal activity and microbiota-derived molecules
D’Alessandro, G., Marrocco, F., & Limatola, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1011129 · Cited by 31
“The pruning activity in this brain region is not mediated by CX3CR1 (50), which, however, contributes to the pruning of the barrel cortex and hippocampus (51, 52), indicating a spatial functional heterogeneity of microglia for the same activity.”
BackgroundAghaie, C. I., Hausknecht, K. A., Wang, R., Dezfuli, P. H., Haj‐Dahmane, S., Kane, C. J. M., Sigurdson, W. J., & Shen, R. (2019) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14275 · Cited by 30
“…for the innate immune response and apoptosis, they also play an important role in surveying and maintaining synaptic function in normal conditions as well as in synaptic maturation and pruning during development (Barron, 1995, Bilimoria and Stevens, 2015, Harry, 2013, Hoshiko et al., 2012).”
BackgroundDual functions of microglia in the formation and refinement of neural circuits during development
Konishi, H., Kiyama, H., & Ueno, M. (2018) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2018.09.009 · Cited by 31
“…include growth factors and neurotrophins, such as basic fibroblast growth factor (bFGF) (Morgan et al., 2004), insulin-like growth factor-1 (IGF-1) (Hristova et al., 2010; Chhor et al., 2013; Ueno et al., 2013; Wlodarczyk et al., 2017), nerve growth factor (NGF) (Elkabes et al., 1996; Frade and…”
BackgroundInfluentialThe Microglial Response to Neurodegenerative Disease
Song, W. M., & Colonna, M. (2018) · Advances in immunology · doi:10.1016/bs.ai.2018.04.002 · Cited by 30
Deivasigamani, S., Miteva, M. T., Natale, S., Gutierrez‐Barragan, D., Basilico, B., Angelantonio, S. D., Weinhard, L., Molotkov, D., Deb, S., Pape, C., et al. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad313 · Cited by 28
Loss of P2Y12 Has Behavioral Effects in the Adult Mouse
Lowery, R. L., Mendes, M. S., Sanders, B. T., Murphy, A. J., Whitelaw, B. S., Lamantia, C. E., & Majewska, A. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041868 · Cited by 25
“An intrinsic GFP signal was used to visualize microglia, as in [7].”
BackgroundMethodInfluentialEarly Life Events and Maturation of the Dentate Gyrus: Implications for Neurons and Glial Cells
Aniol, V. A., Манолова, А. О., & Gulyaeva, N. V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084261 · Cited by 28
“At this stage, microglia begin to participate in the neuronal net formation by synaptic pruning [74,96,97].”
BackgroundAssaying Microglia Functions In Vitro
Maguire, E., Connor‐Robson, N., Shaw, B., O’Donoghue, R., Stöberl, N., & Hall‐Roberts, H. (2022) · Cells · doi:10.3390/cells11213414 · Cited by 31
Carrier, M., Guilbert, J., Lévesque, J.-P., Tremblay, M., & Desjardins, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.595002 · Cited by 23
Occelli, F., Lameth, J., Adenis, V., Huetz, C., Lévêque, P., Jay, T. M., Edeline, J., & Mallat, M. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.06.002 · Cited by 23
Synaptic pruning by microglia: lessons from genetic studies in mice
de Deus, J. L., Faborode, O. S., & Nandi, S. (2024) · Developmental Neuroscience · doi:10.1159/000541379 · Cited by 23
“However, slice electrophysiology approaches reveal that CX3CR1 does not play a role in TC presynaptic function but is rather important for functional maturation of TC post-synapses in layer IV of the barrel cortex at P5 – P9 [54].”
Acute ethanol exposure rapidly alters cerebellar and cortical microglial physiology
Stowell, R. D., & Majewska, A. K. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14706 · Cited by 22
“Indeed, exposure to EtOH during the brain growth spurt has been shown to result in selective loss of Purkinje neurons, leading to motor deficits later in life (Idrus & Napper, 2012; Topper, Baculis, & Valenzuela, 2015).”
BackgroundStrategies for Manipulating Microglia to Determine Their Role in the Healthy and Diseased Brain
Parajuli, B., & Koizumi, S. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03742-6 · Cited by 25
“In support of this, postnatal CX3CR1 knockout mice have been shown to have delayed recruitment of microglia to the developing hippocampus and somatosensory cortex, with a delay of several days [21, 22].”
BackgroundWhen glia meet induced pluripotent stem cells (iPSCs)
Li, L., & Shi, Y. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103565 · Cited by 24
Microglia as a Hub for Suicide Neuropathology: Future Investigation and Prevention Targets
de Andrade, E. G., Ibáñez, F. G., & Tremblay, M. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.839396 · Cited by 22
“During postnatal development, CX3CR1 is required for microglial recruitment to the cortex and maturation of postsynaptic glutamate receptors in female and male mice (Hoshiko et al., 2012).”
BackgroundSalcido, F. A. M., Torres-Flores, M. I., Ordaz, B., & Peña‐Ortega, F. (2022) · Glia · doi:10.1002/glia.24185 · Cited by 21
“…show, these modifications in the organization of the CA3 circuit may arise in the early stages of postnatal development, a critical period for microglia–neuron interaction through the fractalkine pathway (Arnoux & Audinat, 2015; Hoshiko et al., 2012; Paolicelli et al., 2011; Zhan et al., 2014).”
BackgroundMethodResultInfluentialJagadapillai, R., Qiu, X., Ojha, K., Li, Z., El-Baz, A. S., Zou, S., Gozal, E., & Barnes, G. N. (2022) · Cells · doi:10.3390/cells11142211 · Cited by 25
Spiteri, A. G., Wishart, C. L., & King, N. J. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.600822 · Cited by 31
“Although microglia can prune superfluous synapses, they can also promote the formation of new ones (37, 72).”
BackgroundBivona, G., Iemmolo, M., Piccoli, T., Agnello, L., Sasso, B. L., Ciaccio, M., & Ghersi, G. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11195498 · Cited by 20
“Throughout the central nervous system (CNS), FKN is mainly expressed in the hippocampus [13], where it interacts with its receptor CX3CR1, which is expressed by microglia and neurons [14].”
BackgroundCo-Culturing Microglia and Cortical Neurons Differentiated from Human Induced Pluripotent Stem Cells
Lopez-Lengowski, K., Kathuria, A., Gerlovin, K., & Karmacharya, R. (2021) · Journal of Visualized Experiments · doi:10.3791/62480 · Cited by 19
The Dual Nature of Microglia in Alzheimer’s Disease: A Microglia-Neuron Crosstalk Perspective
Xie, Z., Meng, J., Wu, Z., Nakanishi, H., Hayashi, Y., Kong, W., Lan, F., Narengaowa, Yang, Q., Qing, H., et al. (2023) · The Neuroscientist · doi:10.1177/10738584211070273 · Cited by 19
Chen, R., Routh, B. N., Gaudet, A. D., & Fonken, L. K. (2023) · Journal of Biological Rhythms · doi:10.1177/07487304231178950 · Cited by 21
“Microglia dysfunctions impair activity-dependent synaptic pruning (Hoshiko et al., 2012; Schafer et al., 2012).”
Akinlaja, Y. O., & Nishiyama, A. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1418100 · Cited by 23
“…is detected around P5, shortly followed by the invasion of microglia from the barrel septum into the barrel hollow where the thalamocortical axons from each whisker input are clustered (Hoshiko et al., 2012), and its receptor CX3CR1 is needed for the postsynaptic maturation of glutamate receptors.”
BackgroundWhat the Spectrum of Microglial Functions Can Teach us About Fetal Alcohol Spectrum Disorder
Wong, E. L., Stowell, R. D., & Majewska, A. K. (2017) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2017.00011 · Cited by 21
“…during early postnatal development and promote pruning of excess synapses; failure of infiltration results in a transient hyperconnectivity which normalizes, presumably through non-microglial specific mechanisms, in adulthood (Paolicelli et al., 2011; Hoshiko et al., 2012; Arnoux et al., 2013).”
BackgroundInfluentialAge-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases
Eugenín, J. L., Bernhardi, L. E.-V., & Rommy von Bernhardi, M. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1249320 · Cited by 19
Arcuri, C., Mecca, C., Giambanco, I., & Donato, R. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.04.005 · Cited by 19
“Synaptic maturation is also influenced by microglia during development, and the CX3CL1–CX3CR1 axis participates in this event (Hoshiko et al., 2012).”
BackgroundRole of Microglia in Central Nervous System Development and PlasticityPreprint
Schafer, D. P., Stevens, B., Bennett, M. L., & Bennett, F. C. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041810 · Cited by 19
Wang, W., Wang, J., Tang, Q., Zhu, X., Zhu, R., Cui, D., Wei, C., Liu, X., Liu, X., Ran, S., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.02.053 · Cited by 17
Mendiola, A. S., Church, K. A., Cardona, S. M., Vanegas, D., Garcia, S. A., Macklin, W. B., Lira, S. A., Ransohoff, R. M., Kokovay, E., Lin, C. A., et al. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15616 · Cited by 15
Liu, C., Gao, X., Shi, R., Wang, Y., He, X., Du, H., Hu, B., Jiao, J., Liu, C., & Teng, Z. (2023) · Cell Proliferation · doi:10.1111/cpr.13439 · Cited by 16
Bertot, C., Groc, L., & Avignone, E. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.03.006 · Cited by 17
Self-citationLee, J., Lee, S., Ryu, Y., Lee, D., Kim, S., Seo, J., Oh, E.-J., Paek, S. H., Kim, S. U., Ha, C., et al. (2019) · Glia · doi:10.1002/glia.23638 · Cited by 16
Microglia, synaptic dynamics and forgetting
Wang, C., Wang, L., & Gu, Y. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.06.005 · Cited by 20
La microglie : des cellules immunitaires qui sculptent et contrôlent les synapses neuronales
Audinat, É., & Arnoux, I. (2014) · médecine/sciences · doi:10.1051/medsci/20143002012 · Cited by 17
“Ce retard de recrutement de la microglie aux sites des synapses thalamo-corticales s’accompagne d’un retard de maturation des propriétés de ces synapses qui se caractérise en particulier par un défaut dans l’expression fonctionnelle des récepteurs postsynaptiques du glutamate [36].”
Self-citationPathogenesis and therapeutic applications of microglia receptors in Alzheimer’s disease
Fu, J., Wang, R., He, J., Liu, X., Wang, X., Yao, J., Liu, Y., Ran, C., Ye, Q., & He, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1508023 · Cited by 17
Early life adversity across different cell- types in the brain
Warhaftig, G., Almeida, D. M., & Turecki, G. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105113 · Cited by 20
d’Errico, P., Früholz, I., Meyer‐Luehmann, M., & Vlachos, A. (2025) · Brain stimulation · doi:10.1016/j.brs.2025.03.012 · Cited by 19
Altered trajectories of neurodevelopment and behavior in mouse models of Rett syndrome
Smith, E. S., Smith, D. R., Eyring, C., Braileanu, M., Smith-Connor, K., Tan, Y. E., Fowler, A., Hoffman, G. E., Johnston, M. V., Kannan, S., et al. (2018) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2018.11.007 · Cited by 17
Yamawaki, Y., Wada, Y., Matsui, S., & Ohtsuki, G. (2022) · Current Research in Neurobiology · doi:10.1016/j.crneur.2022.100028 · Cited by 16
Microglia in the Primary Somatosensory Barrel Cortex Mediate Trigeminal Neuropathic Pain
Wang, Y., Cao, P., Mei, L., Yin, W., Mao, Y., Niu, C., Zhang, Z., & Tao, W. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.05.034 · Cited by 17
Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex
Blagburn-Blanco, S. V., Chappell, M. S., Biase, L. M. D., & DeNardo, L. A. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.965756 · Cited by 16
“, 2022), synapse maturation (Hoshiko et al., 2012), and synapse refinement (Schafer et al.”
BackgroundMilinkeviciute, G., Chokr, S. M., Castro, E. M., & Cramer, K. S. (2021) · The Journal of Comparative Neurology · doi:10.1002/cne.25150 · Cited by 16
“…contributions to microglial migration (Cardona et al., 2006; Liang et al., 2009; Ruitenberg et al., 2008), it is possible that loss of fractalkine signaling prevents microglia from reaching the points of synaptic pruning or leads to a delay in microglial recruitment (Hoshiko et al., 2012).”
BackgroundInfluentialStothert, A. R., & Kaur, T. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.694292 · Cited by 15
“…components to CNS development, including neuronal development and maturation (both through the death of neurons during development, and the protection of neurons during life; Ueno et al., 2013), development of neuronal circuits, and synaptic maturation (Hoshiko et al., 2012; Zhan et al., 2014).”
BackgroundSculpting Cerebral Cortex with Serotonin in Rodent and Primate
Vitalis, T., & Verney, C. (2017) · InTech eBooks · doi:10.5772/intechopen.69000 · Cited by 14
Lowery, R. L., Cealie, M. Y., Lamantia, C. E., Mendes, M. S., Drew, P. D., & Majewska, A. K. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24808 · Cited by 14
Watson, Z., & Tang, S. (2022) · Cells · doi:10.3390/cells11121943 · Cited by 13
“CX3CR1 is a chemokine receptor expressed only on microglia in the CNS and the binding of its only known ligand, fractalkine (CX3CL1), promotes microglial recruitment during the development of the hippocampus [34], and global knockdown of CX3CR1 and CX3CL1 showed that they are required for microglial pruning of synapse…”
BackgroundCealie, M. Y., Douglas, J. C., Le, L., VonKaenel, E. D., McCall, M. N., Drew, P. D., & Majewska, A. K. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1176581 · Cited by 11
Neuronal control of microglia through the mitochondria
Pereira-Santos, A. R., Candeias, E., Magalhães, J. D., Empadinhas, N., Esteves, A. R., & Cardoso, S. M. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167167 · Cited by 13
Microglia and infiltrating macrophages in ictogenesis and epileptogenesis
Bröer, S., & Pauletti, A. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1404022 · Cited by 14
Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy
Wątroba, M., Grabowska, A. D., & Szukiewicz, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147527 · Cited by 13
“− / − /GFP/GFP Recently, a key role was a tt ributed to synaptic pruning dependent on microglia, which phagocytize inactive synapses during the postnatal maturation of the brain [93]. are detected at postnatal day 9 [96].”
BackgroundPerineuronal Net Alterations Following Early-Life Stress: Are Microglia Pulling Some Strings?
Rahimian, R., Belliveau, C., Simard, S., Turecki, G., & Mechawar, N. (2024) · Biomolecules · doi:10.3390/biom14091087 · Cited by 18
“For instance, neuroglial interactions through the CX3C motif chemokine ligand 1 (CX3CL1) and the CX3C chemokine receptor 1 (CX3CR1) play a prominent role in complement-independent synaptic elimination [37,38].”
BackgroundMicrogliosis: a double‐edged sword in the control of food intake
Salvi, J., Andreoletti, P., Audinat, É., Balland, É., Fradj, S. B., Cherkaoui‐Malki, M., Heurtaux, T., Liénard, F., Nédélec, E., Rovère, C., et al. (2022) · FEBS Journal · doi:10.1111/febs.16583 · Cited by 16
Lou, L., Yu, T., Dai, Y., Zhao, S., Feng, S., Xu, J., & Wen, Z. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2203273119 · Cited by 13
Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia
Chamera, K., Szuster-Głuszczak, M., & Basta‐Kaim, A. (2021) · Pharmacological Reports · doi:10.1007/s43440-021-00269-5 · Cited by 12
“Other research revealed that Cx3cr1−/− knockouts exhibited alterations in postnatal functional maturation of thalamocortical synapses [143].”
ResultA decade of diverse microglial-neuronal physical interactions in the brain (2008–2018)
Uweru, J. O., & Eyo, U. B. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.01.001 · Cited by 13
“These aberrations were correlated with a transient reduction in microglial density in CX3CR1-deficient hippocampi [25, 42].”
BackgroundUndisturbed climbing fiber pruning in the cerebellar cortex of CX 3 CR1 ‐deficient mice
Kaiser, N. C., Pätz, C., Brachtendorf, S., Eilers, J., & Bechmann, I. (2020) · Glia · doi:10.1002/glia.23842 · Cited by 12
“No difference was observed between WT and KO mice (Wilcoxon rank test) Scale bar = 100 pA and 10 ms the hippocampus (Hoshiko et al., 2012; Paolicelli et al., 2011).”
BackgroundMethodInfluentialFeng, L., Lo, H., Hong, Z., Zheng, J., Yan, Y., Ye, Z., Chen, X., & Pan, X. (2023) · Glia · doi:10.1002/glia.24422 · Cited by 12
“…of microglia that responds to α-Syn toxic- ity and a target for preventing neurologic degeneration in PD. Initiated through cells, the microglial phagocytosis internalized the engulfed large particles (typically ≥5 μm) and combined with vesicles to reduce α-Syn deposition (Janda et al., 2018).”
BackgroundBelliveau, C., Rahimian, R., Fakhfouri, G., Hosdey, C., Simard, S., Davoli, M. A., Mirault, D., Giros, B., Turecki, G., & Mechawar, N. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.12.013 · Cited by 14
Spatial impact of microglial distribution on dynamics of dendritic spines
Iida, T., Tanaka, S., & Okabe, S. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14325 · Cited by 12
“Consistent with this idea, a decrease in microglial density has been proposed to reduce synapse pruning and maturation (Hoshiko et al., 2012; Schafer et al., 2012), and depletion of microglia decreased the spine turnover (Parkhurst et al.”
BackgroundInterleukin-1β and interleukin-6 affect electrophysiological properties of thalamic relay cells
Samios, V. N., & Inoue, T. (2014) · Neuroscience Research · doi:10.1016/j.neures.2014.06.011 · Cited by 11
Wei, H.-R., Tang, L. F., Yang, X., Chen, C., Li, L.-X., Mao, Y., Wang, D., Kang, F., Qun, S., Zhang, Z., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113804 · Cited by 10
Vecchiarelli, H. A., Lopes, L. T., Paolicelli, R. C., Stevens, B., Wake, H., & Tremblay, M. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_11 · Cited by 10
Ageing-related changes in the regulation of microglia and their interaction with neurons
Rommy von Bernhardi, M., & Eugenín, J. L. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110241 · Cited by 10
Brett, C. A., Carroll, J. B., & Gabriele, M. L. (2021) · Glia · doi:10.1002/glia.24134 · Cited by 10
“Deficiency or loss-offunction of fractalkine signaling impairs occupancy and functional development of barrel fields (Gunner et al., 2019; Hoshiko et al., 2012), as well as synaptic-dendritic spine pruning in the hippocampus (Paolicelli et al., 2011; Paolicelli et al., 2014).”
BackgroundMethodResultInfluentialClearing Your Mind: Mechanisms of Debris Clearance After Cell Death During Neural Development
Liu, K. E., Raymond, M. H., Ravichandran, K. S., & Kucenas, S. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-110920-022431 · Cited by 10
Headmasters: Microglial regulation of learning and memory in health and disease
Weinhard, L., d’Errico, P., & Tay, T. L. (2018) · AIMS molecular science · doi:10.3934/molsci.2018.1.63 · Cited by 11
“Lack of CX3CR1 also dysregulated the increase in AMPA receptors at glutamatergic synapses of the barrel cortex during CNS development [21].”
Sobierajski, E., Lauer, G., Aktas, M., Beemelmans, C., Beemelmans, C., Meyer, G., & Wahle, P. (2021) · The Journal of Comparative Neurology · doi:10.1002/cne.25280 · Cited by 10
“Inmouse somatosensory cortex, microglia cells settle in layer 4 from P5 onwards, rarely dividing at this age, and more ramified morphologies develop until P7 (Arnoux et al., 2013; Hoshiko et al., 2012).”
BackgroundMicroglia shape the embryonic development of mammalian respiratory networks
Cabirol, M.-J., Cardoit, L., Courtand, G., Mayeur, M.-E., Simmers, J., Pascual, O., & Thoby‐Brisson, M. (2022) · eLife · doi:10.7554/elife.80352 · Cited by 12
Li, J., Wang, Z., Zhang, Y., Li, Y., Feng, L., Wang, J., Wang, J., Zhou, Z., Zhang, Y., & Chang, X. (2024) · Environmental Research · doi:10.1016/j.envres.2024.118602 · Cited by 12
Petit, M., Weber-Delacroix, E., Lanthiez, F., Barthélémy, S., Guillou, N., Firpion, M., Bonduelle, O., Hume, D. A., Combadière, C., & Boissonnas, A. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114847 · Cited by 9
Minocycline prevents hypoxia-induced seizures
Fukushi, I., Ikeda, K., Takeda, K., Yoshizawa, M., Kono, Y., Hasebe, Y., Pokorski, M., & Okada, Y. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1006424 · Cited by 9
“, 2015), neurotransmission (Hoshiko et al., 2012), and synaptic plasticity (Rogers et al.”
BackgroundMolecular mechanisms mediating involvement of glial cells in brain plastic remodeling in epilepsy
Хаспеков, Л. Г., & Frumkina, L. E. (2017) · Biochemistry (Moscow) · doi:10.1134/s0006297917030178 · Cited by 10
“The deficit of fractalkine signaling suppressed microglia prop agation in the CNS and conversion of the NMDA recep tor subunit GluN2B into GluN2A subunit during synapse development [53, 54].”
BackgroundDeletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity
Cote, J. L., Argetsinger, L. S., Flores, A., Rupp, A. C., Cline, J. M., DeSantis, L. C., Bedard, A. H., Bagchi, D. P., Vander, P. B., Cacciaglia, A. M., et al. (2020) · Diabetes · doi:10.2337/db20-0687 · Cited by 8
Clabough, E. B. D., Ingersoll, J., Reekes, T. H., Gleichsner, A. M., & Ryan, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010290 · Cited by 9
Microglial Modulation of Synaptic Maturation, Activity, and Plasticity
Pinto, M. J., Ragozzino, D., Bessis, A., & Audinat, É. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_12 · Cited by 9
The fate of neuronal synapse homeostasis in aging, infection, and inflammation
Tacke, C., Landgraf, P., Dieterich, D. C., & Kröger, A. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00466.2024 · Cited by 9
Nelson, N., Miller, V. K., & Broadie, K. S. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1540052 · Cited by 11
Microglia in the pathogenesis of depression, insomnia and their comorbidity
Liu, F., Guo, D., Gao, T., Diao, M., & Han, Y. (2023) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2023.100030 · Cited by 8
The Cl− transporter ClC-7 is essential for phagocytic clearance by microglia
Iyer, H., & Talbot, W. S. (2024) · Journal of Cell Science · doi:10.1242/jcs.261616 · Cited by 9
Epigenomic and transcriptional determinants of microglial cell identity
Gosselin, D. (2020) · Glia · doi:10.1002/glia.23787 · Cited by 7
Microglial Pten safeguards postnatal integrity of the cortex and sociability
Zhou, X., Wei, J., Li, L., Shu, Z., You, L., Liu, Y., Zhao, R., Yao, J., Wang, J., Luo, M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1059364 · Cited by 7
“Ablation of CX3CR1, a chemokine receptor that is expressed by microglia and mediates microglia-neuron interactions (8), leads to impaired synapse maturation, decreased functional brain connectivity, and autism-like abnormal behaviors (9, 10).”
BackgroundDeveloping and Mature Synapses
Tremblay, M., Paolicelli, R. C., Stevens, B., Wake, H., & Bessis, A. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1429-6_9 · Cited by 7
Mendoza-Romero, H. N., Biddinger, J. E., Bedenbaugh, M. N., & Simerly, R. B. (2024) · eLife · doi:10.7554/elife.101391 · Cited by 8
“…; Valdearcos et al., 2014 ; Baufeld et al., 2016 ; Valdearcos et al., 2017 ) and multiple lines of evidence support an important role for microglia in mediating key aspects of neural circuit development ( Checchin et al., 2006 ; Hoshiko et al., 2012 ; Li et al., 2012 ; Hagemeyer et al., 2017 ).”
Xie, M., Wang, T., Feng, J., Ma, D., Feng, L., & Hao, Y. (2025) · Current Neuropharmacology · doi:10.2174/1570159x23666250225091729 · Cited by 7
“This is due to the delayed recruitment of microglia to mature sites of thalamocortical synapses [125].”
Liong, S., Choy, K. H. C., Luca, S. N. D., Liong, F., Coward‐Smith, M., Oseghale, O., Miles, M. A., Vlahos, R., Valant, C., Nithianantharajah, J., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.06.025 · Cited by 6
Stoessel, M. B., Stowell, R. D., Lowery, R. L., Le, L., Vu, A. N., Whitelaw, B. S., & Majewska, A. K. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.03.036 · Cited by 7
Macrophage Development and Function
Makdissi, N. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3437-0_1 · Cited by 5
Advances in microglia cellular models: focus on extracellular vesicle production
Ceccarelli, L., Marchetti, L., Giacomelli, C., & Martini, C. (2021) · Biochemical Society Transactions · doi:10.1042/bst20210203 · Cited by 5
Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage
Pawelec, P., Sypecka, J., Zalewska, T., & Ziemka‐Nałęcz, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158287 · Cited by 6
“Fractalkine seems to contribute to the remodeling of neuronal circuits and the maturation of excitatory glutamatergic synapses during postnatal development [23,54,55].”
BackgroundRiquier, A. J., & Sollars, S. I. (2022) · Developmental Neurobiology · doi:10.1002/dneu.22904 · Cited by 5
“Age-dependent innervation and synapse reduction have been observed in multiple brain regions such as the cerebellum (Hashimoto & Kano, 2003, 2013), cortex (Hoshiko et al., 2012; Low et al., 2008; Mallya et al., 2019), and brainstem (Mangold & Hill, 2008; Sollars et al., 2006).”
BackgroundWatters, J. J., & Pocock, J. M. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1429-6_3 · Cited by 5
Contemporary insights into neuroimmune interactions across development and aging
Yeo, X. Y., Choi, Y., Hong, Y., Kwon, H. N., & Jung, S. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1611124 · Cited by 5
Remyelinating strategies: What can be learned from normal brain development
Shelestak, J., Irfan, M., & DeSilva, T. M. (2022) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2022.102290 · Cited by 4
Metadata
- Authors
- Hoshiko, M., Arnoux, I., Avignone, E., Yamamoto, N., & Audinat, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- The University of Osaka (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-10-24
- Volume
- 32
- Issue
- 43
- Pages
- 15106-15111
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6704837
- OpenAlex
- W1996055705
- Cited by
- 384
- References
- 33
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 36 · 2023: 29 · 2022: 40 · 2021: 41 · 2020: 35 · 2019: 39 · 2018: 30 · 2017: 23 · 2016: 19 · 2015: 14 · 2014: 22 · 2013: 22
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Uehara Memorial Foundation
- Ministry of Education, Culture, Sports, Science and Technology (23115102)
- Japan Society for the Promotion of Science (20021018)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- CX3CR1, fractalkine, microglia, synapse maturation, thalamocortical synapses, barrel cortex, postnatal development, microglial recruitment, glutamate receptors, microglia-neuron interaction, somatosensory cortex
- MeSH terms
- CX3C Chemokine Receptor 1, Age Factors, Animals, Animals, Newborn, Developmental Disabilities, Electric Stimulation, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Somatosensory Cortex, Synapses, Thalamus, Microglia, Gene Expression Regulation, Developmental, Excitatory Amino Acid Antagonists, Statistics, Nonparametric, GABA Antagonists, Excitatory Postsynaptic Potentials, Receptors, Chemokine, Green Fluorescent Proteins, Serotonin Plasma Membrane Transport Proteins, Mice, Chemokine CX3CL1, In Vitro Techniques
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