The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
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).”
Background
Cited by
Sorted by citations
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
“CX3CR1-CX3CL1 interactions are also required for functional maturation of thalamocortical synapses (72).”
BackgroundMicroglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599
“Recent work has shown that mice lackingCX3CR1 have delayed invasion of the cortical barrel fields by microglia, and a transient delay in the normally observed AMPA receptor subunit switching in thalamocortical barrel cortex synapses (Hoshiko et al., 2012).”
BackgroundMicroglia and macrophages in brain homeostasis and disease
Li, Q., & Barres, B. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.125 · Cited by 1,999
A polarizing question: do M1 and M2 microglia exist?
Ransohoff, R. M. (2016) · Nature Neuroscience · doi:10.1038/nn.4338 · Cited by 1,573
Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction
Weinhard, L., di Bartolomei, G., Bolasco, G., Machado, P., Schieber, N. L., Neniskyte, U., Exiga, M., Vadisiute, A., Raggioli, A., Schertel, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03566-5 · Cited by 790
Microglia Modulate Wiring of the Embryonic Forebrain
Squarzoni, P., Oller, G., Hoeffel, G., Pont‐Lezica, L., Rostaing, P., Low, D., Bessis, A., Ginhoux, F., & Garel, S. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.042 · Cited by 697
Microglia: Dynamic Mediators of Synapse Development and Plasticity
Wu, Y., Dissing-Olesen, L., MacVicar, B. A., & Stevens, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.008 · Cited by 661
“Lack of CX3CR1 has been associated with reduced synaptic pruning in other brain regions [9,14].”
BackgroundNew insights on the role of microglia in synaptic pruning in health and disease
Hong, S., Dissing-Olesen, L., & Stevens, B. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.12.004 · Cited by 557
Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K., & Tremblay, M. (2017) · The Journal of Physiology · doi:10.1113/jp272134 · Cited by 562
“It is necessary for the timely recruitment of microglial cells into the early postnatal hippocampus and cerebral cortex (Hoshiko et al. 2012; Ueno et al. 2013; Paolicelli et al. 2014).”
BackgroundThe Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516
Sublime Microglia: Expanding Roles for the Guardians of the CNS
Salter, M. W., & Beggs, S. (2014) · Cell · doi:10.1016/j.cell.2014.06.008 · Cited by 531
“In CX3CR1 null mice, the invasion of microglial cells to the barrel centers is delayed by several days, as is maturation of the thalamocortical synapses (Hoshiko et al., 2012).”
Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function
Lenz, K. M., & Nelson, L. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00698 · Cited by 517
“CX3CR1−/− mice have a transiently decreased microglia density in the hippocampus and delayed microglia entry into the barrel cortices and social behavior (11, 12, 62).”
BackgroundBidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459
Microglia morphophysiological diversity and its implications for the CNS
Vidal-Itriago, A., Radford, R. A. W., Aramideh, J. A., Maurel, C., Scherer, N. M., Don, E. K., Lee, A., Chung, R. S., Graeber, M. B., & Morsch, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.997786 · Cited by 451
Microglia: Architects of the Developing Nervous System
Frost, J. L., & Schafer, D. P. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.02.006 · Cited by 385
“In more recent studies, transient reductions in microglia numbers in the hippocampus or barrel cortex due to a genetic deletion of CX3CR1 (CX3CR1 KO) resulted in delayed maturation of structural and functional synapses [55, 56].”
BackgroundFactors regulating microglia activation
Kierdorf, K., & Prinz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00044 · Cited by 360
“In addition, another study reported that CX3CR1-deficient animals exhibited an inhibition in microglial recruitment to forming synapses in the barrel field of the somatosensory cortex, leading to an abnormal synapse formation in this area (Hoshiko et al., 2012).”
BackgroundCell-to-cell Communication by Extracellular Vesicles: Focus on Microglia
Paolicelli, R. C., Bergamini, G., & Rajendran, L. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.04.003 · Cited by 338
Microglia in the Retina: Roles in Development, Maturity, and Disease
Silverman, S. M., & Wong, W. T. (2018) · Annual Review of Vision Science · doi:10.1146/annurev-vision-091517-034425 · Cited by 364
Neuron–glia crosstalk in health and disease: fractalkine and CX 3 CR1 take centre stage
Sheridan, G. K., & Murphy, K. J. (2013) · Open Biology · doi:10.1098/rsob.130181 · Cited by 358
Neuron-glia signaling in synapse elimination
Wilton, D. K., Dissing-Olesen, L., & Stevens, B. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050306 · Cited by 332
Stowell, R. D., Sipe, G. O., Dawes, R. P., Batchelor, H. N., Lordy, K. A., Whitelaw, B. S., Stoessel, M. B., Bidlack, J. M., Brown, E., Sur, M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0514-0 · Cited by 321
Fractalkine regulation of microglial physiology and consequences on the brain and behavior
Paolicelli, R. C., Bisht, K., & Tremblay, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00129 · Cited by 331
“However, the defect was transient, without any remaining difference in the decay time of NMDAR-mediated responses at P27– P33 (Hoshiko et al., 2012).”
BackgroundInfluentialSensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling
Gunner, G., Cheadle, L., Johnson, K. M., Ayata, P., Badimon, A., Mondo, E., Nagy, M. A., Liu, L., Bemiller, S. M., Kim, K.-W., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0419-y · Cited by 318
Microglia, seen from the CX3CR1 angle
Wolf, Y., Yona, S., Kim, K.-W., & Jung, S. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00026 · Cited by 316
Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders
Neniškytė, U., & Gross, C. T. (2017) · Nature reviews. Neuroscience · doi:10.1038/nrn.2017.110 · Cited by 322
The identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308
Microglia–Neuron Communication in Epilepsy
Eyo, U. B., Murugan, M., & Wu, L. (2016) · Glia · doi:10.1002/glia.23006 · Cited by 300
“Because emerging data suggest that microglia as the brain resident immune cells play crucial roles in neural development (Eyo and Dailey, 2013; Hoshiko et al., 2012; Paolicelli et al., 2011; Paolicelli and Gross, 2011; Pont-Lezica et al., 2011; Schafer et al., 2012; Schlegelmilch et al., 2011; Squarzoni et al., 2014),…”
BackgroundInfluentialActivation of Neuronal NMDA Receptors Triggers Transient ATP-Mediated Microglial Process Outgrowth
Dissing-Olesen, L., LeDue, J. M., Rungta, R. L., Hefendehl, J. K., Choi, H. B., & MacVicar, B. A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0405-14.2014 · Cited by 286
“However, our study does not exclude the possibility that CX3CR1 might play a role during development where CX3CR1 deficiency has been demonstrated to result in reduced microglial numbers, impaired switching of GluN2B-to-GluN2A, and delays in synaptic maturation (Paolicelli et al., 2011; Hoshiko et al., 2012).”
BackgroundMicroglia and the aging brain: are senescent microglia the key to neurodegeneration?
Angelova, D. M., & Brown, D. R. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14860 · Cited by 262
Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities
Hemonnot, A.-L., Hua, J., Ulmann, L., & Hirbec, H. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00233 · Cited by 298
“CX3CL1-CX3CR1 is a critical signaling pathway during development as shown by the delay of glutamatergic synapse maturation (Paolicelli et al., 2011; Hoshiko et al., 2012) and functional consequences in adult synapses (Basilico et al.”
BackgroundMicroglia in CNS development: Shaping the brain for the future
Mosser, C., Baptista, S., Arnoux, I., & Audinat, É. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.002 · Cited by 289
“Synaptic refinement At postnatal stages, microglial cells contribute to the refinement of synaptic networks and to the functional maturation of synapses (Hoshiko et al., 2012; Paolicelli et al., 2011; Schafer et al., 2012; Zhan et al., 2014).”
InfluentialSelf-citationMicroglia and aging: the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes
Mecca, C., Giambanco, I., Donato, R., & Arcuri, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010318 · Cited by 258
“Moreover, microglial cell infiltration into the barrel centers of the developing somatosensory cortex, that normally occurs around postnatal day 5, is delayed by a few days in Cx3cr1-/- GFP/GFP mice, even if no differences are detected at postnatal day 9 [143].”
BackgroundShaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions
Cserép, C., Pósfai, B., & Dénes, Á. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.007 · Cited by 256
“…as THIK-1, that regulate microglial membrane potential and receptor signaling; mechanisms that allow ion exchange between the cell and the extracellular matrix (e.g., via P2Y2R); and anchoring structures such as b1-integrin (Haynes et al., 2006; Hristovska and Pascual, 2016; Madry et al., 2018a).”
BackgroundAging Microglia—Phenotypes, Functions and Implications for Age-Related Neurodegenerative Diseases
Spittau, B. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00194 · Cited by 270
“Recent reports have contributed to broaden our understanding that microglia capacities in the CNS include several essential features such as synaptic pruning (Stevens et al., 2007; Paolicelli et al., 2011; Hoshiko et al., 2012; Schafer et al., 2012), influencing functions of activated and/or over-activated neurons (Pa…”
BackgroundMicroglia in Brain Development, Homeostasis, and Neurodegeneration
Bohlen, C. J., Friedman, B. A., Dejanovic, B., & Sheng, M. (2019) · Annual Review of Genetics · doi:10.1146/annurev-genet-112618-043515 · Cited by 212
Paolicelli, R. C., & Ferretti, M. T. (2017) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2017.00009 · Cited by 252
“Hoshiko et al. (2012) showed that the lack of the Cx3cr1 was associated with delayed maturation of the developing synapses in the barrel cortex, specifically affecting the NMDAR composition.”
BackgroundCytokines as emerging regulators of central nervous system synapses
Zipp, F., Bittner, S., & Schafer, D. P. (2023) · Immunity · doi:10.1016/j.immuni.2023.04.011 · Cited by 257
Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission
Marinelli, S., Basilico, B., Marrone, M. C., & Ragozzino, D. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.05.017 · Cited by 233
Neuronal synapse formation induced by microglia and interleukin 10
Lim, S.-H., Park, E., You, B., Jung, Y., Park, A.-R., Park, S. G., & Lee, J.-R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081218 · Cited by 224
“functions, including synaptic remodeling, during the development of central nervous systems [12,13,14].”
BackgroundMicroglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
Tay, T. L., Béchade, C., D’Andrea, I., St‐Pierre, M., Henry, M. S., Roumier, A., & Tremblay, M. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00421 · Cited by 217
“…immaturity (Paolicelli et al., 2011; Rogers et al., 2011; Zhan et al., 2014), the maturation of glutamatergic thalamocortical synapses was delayed during postnatal development (Hoshiko et al., 2012), while the positioning of neocortical interneurons was altered prenatally (Squarzoni et al., 2014).”
BackgroundInfluentialMicroglia in multiple sclerosis: Friend or foe
Guerrero, B. L., & Sicotte, N. L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00374 · Cited by 215
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling
Limatola, C., & Ransohoff, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00229 · Cited by 210
“During development, CX3CL1/CX3CR1 signaling contributes to refinement of synaptic elements in varied CNS regions during the postnatal “critical period” (Tremblay et al., 2010; Paolicelli et al., 2011; Hoshiko et al., 2012).”
BackgroundZabel, M. K., Zhao, L., Zhang, Y., Gonzalez, S. R., Ma, W., Wang, X., Fariss, R. N., & Wong, W. T. (2016) · Glia · doi:10.1002/glia.23016 · Cited by 210
“During development, CX3CL1-CX3CR1 signaling influences microglial regulation of neuronal survival (Sierra et al., 2010; Ueno et al., 2013), and synaptic maturation and refinement (Hoshiko et al., 2012; Paolicelli et al., 2011) in the brain.”
BackgroundBidirectional Microglia‐Neuron Communication in the Healthy Brain
Eyo, U. B., & Wu, L. (2013) · Neural Plasticity · doi:10.1155/2013/456857 · Cited by 208
“…reports on defective neuronal development in the hippocampus of fractalkine receptor-deficient mice were extended to the cortex in another study where proper maturation of thalam-ocortical circuits in the barrel cortex of developing mice was shown to require functional fractalkine signaling [44].”
Microglial immune checkpoint mechanisms
Deczkowska, A., Amit, I., & Schwartz, M. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0145-x · Cited by 185
Intersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197
Nemes-Baran, A. D., White, D. R., & DeSilva, T. M. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108047 · Cited by 196
“The fractalkine receptor is only expressed on microglia in the CNS, and CX3CR1:GFPKO/KO mice are one of the most widely used tools to study modulation of synaptic engulfment during early postnatal development (Paolicelli et al., 2011; Zhan et al., 2014; Hoshiko et al., 2012).”
BackgroundHayashi, Y., Koyanagi, S., Kusunose, N., Okada, R., Wu, Z., Tozaki‐Saitoh, H., Ukai, K., Kohsaka, S., Inoue, K., Ohdo, S., et al. (2013) · Scientific Reports · doi:10.1038/srep02744 · Cited by 198
Microglia as Dynamic Cellular Mediators of Brain Function
Wright-Jin, E. C., & Gutmann, D. H. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.08.013 · Cited by 197
Depression as a Glial-Based Synaptic Dysfunction
Rial, D., Lemos, C., Pinheiro, H., Duarte, J. M., Gonçalves, F. Q., Real, J. I., Prediger, R. D., Gonçalves, N., Gomes, C. A., Canas, P. M., et al. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00521 · Cited by 193
“…bi-directional communication between synapses and microglia is best heralded by the synaptic dysfunction observed upon genetic manipulation of microglia function (Roumier et al., 2004; Costello et al., 2011; Hoshiko et al., 2012), which can be direct or involve astrocytes (Pascual et al., 2012).”
BackgroundType-I-interferon-responsive microglia shape cortical development and behavior
Escoubas, C. C., Dorman, L. C., Nguyen, P. T., Lagares-Linares, C., Nakajo, H., Anderson, S. R., Barron, J. J., Wade, S. D., Cuevas, B., Vainchtein, I. D., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.020 · Cited by 179
Microglia as hackers of the matrix: sculpting synapses and the extracellular space
Crapser, J. D., Arreola, M. A., Tsourmas, K. I., & Green, K. N. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00751-3 · Cited by 178
“The CX3CL1-CX3CR1 axis is already well established as a major pathway of neuron-microglia communication that is involved in synaptic pruning and development [38, 269, 270] as well as microglial mobility, motility, and activation [270–272] and therefore seems to be a feasible candidate in the regulation of this process.”
BackgroundLearning and memory … and the immune system
Marin, I., & Kipnis, J. (2013) · Learning & Memory · doi:10.1101/lm.028357.112 · Cited by 166
“Moreover, CX3CR1-deficient microglia demonstrate delayed recruitment to the developing barrel cortex, with a corresponding delay in maturation of the postsynaptic compartment in terms of the AMPA/NMDA receptor ratio as well as the subunit composition of NMDA receptors (Hoshiko et al. 2012).”
Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers
Williams, J. L., Holman, D. W., & Klein, R. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00154 · Cited by 165
“Neurons and microglia both express its receptor, CX3CR1 (Hatori et al., 2002), which regulates memory formation and synaptic plasticity via direct effects on glutamatergic synapses (Hoshiko et al., 2012; for an extensive review, see Sheridan and Murphy, 2013).”
BackgroundComer, A. L., Jinadasa, T., Sriram, B., Phadke, R. A., Kretsge, L. N., Nguyen, T. P. H., Antognetti, G., Gilbert, J. P., Lee, J., Newmark, E., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000604 · Cited by 163
Glia as sculptors of synaptic plasticity
Sancho, L., Contreras, M., & Allen, N. J. (2020) · Neuroscience Research · doi:10.1016/j.neures.2020.11.005 · Cited by 160
A Developmental Analysis of Juxtavascular Microglia Dynamics and Interactions with the Vasculature
Mondo, E., Becker, S. C., Kautzman, A. G., Schifferer, M., Baer, C. E., Chen, J., Huang, E. J., Simons, M., & Schafer, D. P. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.3006-19.2020 · Cited by 153
Zhang, Y., Zhao, L., Wang, X., Ma, W., Lazere, A., Qian, H., Zhang, J., Abu-Asab, M. S., Fariss, R. N., Roger, J. E., et al. (2018) · Science Advances · doi:10.1126/sciadv.aap8492 · Cited by 145
Microglia: Key players in neurodevelopment and neuronal plasticity
Sominsky, L., Luca, S. N. D., & Spencer, S. J. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.11.012 · Cited by 155
Bolton, J. L., Short, A. K., Othy, S., Kooiker, C. L., Shao, M., Gunn, B. G., Beck, J., Bai, X., Law, S. M., Savage, J. C., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110600 · Cited by 158
“Microglia play a key role in synaptic pruning in the developing visual and somatosensory systems (Hoshiko et al., 2012; Miyamoto et al., 2016; Schafer et al., 2012; Sipe et al., 2016), as well as in developing hippocampus (Paolicelli et al.”
BackgroundMicroglia and synapse interactions: fine tuning neural circuits and candidate molecules
Miyamoto, A., Wake, H., Moorhouse, A. J., & Nabekura, J. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00070 · Cited by 147
On place and time: microglia in embryonic and perinatal brain development
Thion, M. S., & Garel, S. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.004 · Cited by 150
Axon Initial Segment–Associated Microglia
Baalman, K., Marin, M. A., Ho, T., Godoy, M. I., Cherian, L., Robertson, C., & Rasband, M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3751-14.2015 · Cited by 129
“…signaling was shown previously to be involved in neuron–microglia communication, synaptic pruning by microglia, microglia migration, hippocampal neurogenesis, and cognitive function (Sierra et al., 2010; Bachstetter et al., 2011; Paolicelli et al., 2011; Rogers et al., 2011; Hoshiko et al., 2012).”
BackgroundFractalkine Signaling and Microglia Functions in the Developing Brain
Arnoux, I., & Audinat, É. (2015) · Neural Plasticity · doi:10.1155/2015/689404 · Cited by 136
“However, the same functional parameters of thalamocortical synapses do not differ between adult CX3CR1 deficient and wild type mice [48] (Arnoux & Audinat, unpublished).”
BackgroundInfluentialSelf-citationDevelopmental Apoptosis Mediates Entry and Positioning of Microglia in the Zebrafish Brain
Casano, A. M., Albert, M., & Peri, F. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.033 · Cited by 135
“For instance, in the mouse, the chemokines CXCL12 and CX3CL1 have been shown to be involved in the recruitment of microglia to specific brain areas, such as the sub-ventricular zone and the barrel centers, respectively (Arnò et al., 2014; Hoshiko et al., 2012).”
BackgroundInfluentialCerebellar microglia are dynamically unique and survey Purkinje neurons in vivo
Stowell, R. D., Wong, E. L., Batchelor, H. N., Mendes, M. S., Lamantia, C. E., Whitelaw, B. S., & Majewska, A. K. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22572 · Cited by 124
“…cerebellar microglia contribute to the developmental pruning of synapses as circuits develop, much like microglial roles elsewhere in the brain (Stevens et al., 2007; Paolicelli et al., 2011; Hoshiko et al., 2012; Schafer et al., 2012; Zhan et al., 2014; Pagani et al., 2015; Sipe et al., 2016).”
BackgroundMethodInfluentialDynamic microglial modulation of spatial learning and social behavior
Torres, L., Danver, J., Ji, K., Miyauchi, J. T., Chen, D., Anderson, M. E., West, B. L., Robinson, J. K., & Tsirka, S. E. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.09.001 · Cited by 133
Microglia: unique and common features with other tissue macrophages
Prinz, M., Tay, T. L., Wolf, Y., & Jung, S. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1267-1 · Cited by 126
“In the developing barrel cortex, CX3CR1-deficient mice exhibit delayed developmental switch of the glutamate receptor subunits GluN2B to GluNA, one of the main features of barrel cortex development [54].”
BackgroundThe Gut-Microglia Connection: Implications for Central Nervous System Diseases
Wang, Y., Wang, Z., Wang, Y., Li, F., Jia, J., Song, X., Qin, S., Wang, R., Jin, F., Kitazato, K., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02325 · Cited by 130
Miao, Y., Zhao, G., Cheng, S., Wang, Z., & Yang, X.-L. (2023) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2023.101169 · Cited by 126
A microglia-cytokine axis to modulate synaptic connectivity and function
Werneburg, S., Feinberg, P. A., Johnson, K. M., & Schafer, D. P. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.002 · Cited by 126
Microglia and Neonatal Brain Injury
Mallard, C. E., Tremblay, M., & Vexler, Z. S. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.023 · Cited by 123
“Phagocytosis of overproduced neurons and weak synapses by microglia, processes that govern brain connectivity, plays key role in organizing brain circuits during the postnatal period (Paolicelli et al., 2011; Hoshiko et al., 2012; Schafer et al., 2012; Bialas and Stevens, 2013; Zhan et al., 2014).”
BackgroundMicroglial control of neuronal activity
Béchade, C., Cantaut-Belarif, Y., & Bessis, A. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00032 · Cited by 134
“…signaling pathway also appears to be involved in synaptic maturation since CX3CR1 deficiency leads to a delay in the maturation of glutamatergic thalamocortical synapses, as well as a transient immature connectivity in the developing hippocampus (Paolicelli et al., 2011; Hoshiko et al., 2012).”
BackgroundMicroglia: Brain cells on the move
Smolders, S., Kessels, S., Vangansewinkel, T., Rigo, J., Legendre, P., & Brône, B. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.04.001 · Cited by 126
Synaptic Elimination in Neurological Disorders
Cardozo, P. L., de Lima, I. B. Q., Maciel, E. M. A., Silva, N. C., Dobránsky, T., & Ribeiro, F. M. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190603170511 · Cited by 115
Kolodziejczak, M., Béchade, C., Gervasi, N., Irinopoulou, T., Banas, S. M., Cordier, C., Rebsam, A., Roumier, A., & Maroteaux, L. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn5003489 · Cited by 113
Fractalkine in the nervous system: neuroprotective or neurotoxic molecule?
Lauro, C., Catalano, M., Trettel, F., & Limatola, C. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12805 · Cited by 120
The Phagocytic Code Regulating Phagocytosis of Mammalian Cells
Cockram, T. O. J., Dundee, J. M., Popescu, A. S., & Brown, G. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.629979 · Cited by 117
“In the brain, soluble fractalkine is released by the metalloprotease ADAM10 on neurons, and may drive migration of microglia to developing neurites for synaptic pruning during circuitry development (19, 20, 35, 36).”
BackgroundMicroglial Dysregulation in OCD, Tourette Syndrome, and PANDAS
Frick, L. R., & Pittenger, C. (2016) · Journal of Immunology Research · doi:10.1155/2016/8606057 · Cited by 114
“More generally, these results suggest that, in some neuropsychiatric disorders in which no marked neurodegeneration occurs, microglial dysregulation may constitute a failure of neuroprotective functions, which may create a vulnerability to neuroinflammation.”
BackgroundMicroglial trogocytosis and the complement system regulate axonal pruning in vivo
Lim, T. K. Y., & Ruthazer, E. S. (2021) · eLife · doi:10.7554/elife.62167 · Cited by 114
LTD-like molecular pathways in developmental synaptic pruning
Piochon, C., Kano, M., & Hansel, C. (2016) · Nature Neuroscience · doi:10.1038/nn.4389 · Cited by 118
Receptors, Ion Channels, and Signaling Mechanisms Underlying Microglial Dynamics
Madry, C., & Attwell, D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.637157 · Cited by 109
“Fractalkine receptor deficiency leads to a transient reduction of microglial number during early postnatal development (12, 13), microglia-mediated neurotoxicity (65– 67), and impaired phagocytosis of apoptotic newborn neurons, thus causing reduced neurogenesis and deficits in synaptic pruning associated with weaker s…”
BackgroundSexual dimorphism of microglia and synapses during mouse postnatal development
Weinhard, L., Neniskyte, U., Vadisiute, A., di Bartolomei, G., Aygün, N., Riviere, L., Zonfrillo, F., Dymecki, S., & Gross, C. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22568 · Cited by 107
“, 2012), and maturation of synapses (Hoshiko et al., 2012; Zhan et al., 2014; Sipe et al., 2016).”
BackgroundMicroglia control glutamatergic synapses in the adult mouse hippocampus
Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., Ferretti, V., Reverte, I., Sanchini, C., Marrone, M. C., et al. (2021) · Glia · doi:10.1002/glia.24101 · Cited by 104
“Overall, these data suggest that microglial depletion is associated with the appearance of immature synaptic features (Basilico et al., 2019; Hoshiko et al., 2012).”
BackgroundInfluentialCurrent Knowledge of Microglia in Traumatic Spinal Cord Injury
Xu, L., Wang, J., Ding, Y., Wang, L., & Zhu, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.796704 · Cited by 112
“Microglia have been demonstrated to modulate neurotransmission and selective activation of microglia enhances excitatory neurotransmission (53, 54).”
BackgroundRole of Microglial Cells in Alzheimer’s Disease Tau Propagation
Španić, E., Horvat, L. L., Hof, P. R., & Šimić, G. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00271 · Cited by 111
“In mouse model lacking CX3CR1, synaptic pruning was reduced, which led to the formation of immature brain and synapses (Paolicelli et al., 2011; Hoshiko et al., 2012).”
BackgroundPicard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B., Abdallah, F., Albanese, N. C., Amrein, I., Vernoux, N., et al. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.07.022 · Cited by 107
Microglia in brain development and regeneration
Mehl, L. C., Manjally, A. V., Bouadi, O., Gibson, E. M., & Tay, T. L. (2022) · Development · doi:10.1242/dev.200425 · Cited by 113
Nakayama, H., Abe, M., Morimoto, C., Iida, T., Okabe, S., Sakimura, K., & Hashimoto, K. (2018) · Nature Communications · doi:10.1038/s41467-018-05100-z · Cited by 103
Arnoux, I., Hoshiko, M., Mandavy, L., Avignone, E., Yamamoto, N., & Audinat, É. (2013) · Glia · doi:10.1002/glia.22503 · Cited by 96
“, the barrel centers) after P5 and that a deficit in this recruitment is associated with an impairment of the functional maturation of these glutamatergic synapses (Hoshiko et al., 2012).”
BackgroundInfluentialSelf-citationThuc, O. L., Blondeau, N., Nahon, J., & Rovère, C. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12855 · Cited by 105
New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective
Pósfai, B., Cserép, C., Orsolits, B., & Dénes, Á. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.04.046 · Cited by 98
Eltokhi, A., Janmaat, I. E., Genedi, M., Haarman, B. C. M., & Sommer, I. E. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24616 · Cited by 102
Pang, Y., Fan, L., Tien, L., Dai, X., Zheng, B., Cai, Z., Lin, R. C. S., & Bhatt, A. (2013) · Brain and Behavior · doi:10.1002/brb3.152 · Cited by 98
“For example, it has been suggested that CX3CL1 may mediate microglia–neuron communication and synaptogenesis (Hoshiko et al. 2012), and several chemokines have recently been identified as potential regulators for OL development and myelination (Patel et al. 2010).”
BackgroundDefective microglial development in the hippocampus of Cx3cr1 deficient mice
Pagani, F., Paolicelli, R. C., Murana, E., Cortese, B., Angelantonio, S. D., Zurolo, E., Guiducci, E., Ferreira, T., Garofalo, S., Catalano, M., et al. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00111 · Cited by 107
“ORIGINAL RESEARCH published: 31 March 2015 doi: 10.3389/fncel.2015.00111 Edited by: Silvia Alboni, University of Modena and Reggio Emilia, Italy Reviewed by: Claudia Verderio, Consiglio Nazionale delle Ricerche, Italy Claudia Eder, University of London, UK Etienne Audinat, Paris Descartes University, France *Correspon…”
BackgroundMethodInfluentialMicroglia shape presynaptic properties at developing glutamatergic synapses
Basilico, B., Pagani, F., Grimaldi, A., Cortese, B., Angelantonio, S. D., Weinhard, L., Gross, C. T., Limatola, C., Maggi, L., & Ragozzino, D. (2018) · Glia · doi:10.1002/glia.23508 · Cited by 100
“It is important to point out that a similar reduction in AMPA/NMDA ratio has been reported in thalamo-cortical synapses in the developing barrel cortex of Cx3cr1 KO mice, where it was associated with a delay in the migration of microglia into the cortical barrels (Hoshiko et al., 2012).”
BackgroundInfluentialMicroglia: Driving critical periods and sexual differentiation of the brain
VanRyzin, J. W., Pickett, L. A., & McCarthy, M. M. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22569 · Cited by 97
“As a result, glutamatergic synapse maturation is delayed (Hoshiko et al., 2012).”
BackgroundNeonatal microglia: The cornerstone of brain fate
Pierre, W. C., Smith, P. L. P., Londoño, I., Chemtob, S., Mallard, C. E., & Lodygensky, G. A. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.08.018 · Cited by 102
“In addition, elimination or reduction of microglia activity impaired maturation of synapses in the hippocampus and thalamocortical synapses of the barrel cortex as evaluated during the first two weeks of life in mice (Hoshiko et al., 2012; Paolicelli et al., 2011).”
MethodCX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity
Sheridan, G. K., Wdowicz, A., Pickering, M., Watters, O., Halley, P., O’Sullivan, N. C., Mooney, C. M., O’Connell, D. J., Oâ€TMConnor, J. J., & Murphy, K. J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00233 · Cited by 93
“…traditional roles in inflammation and disease (Hopkins and Rothwell, 1995; Rothwell and Hopkins, 1995; Reichenberg et al., 2001; Pollmächer et al., 2002; Wilson et al., 2002; Adler and Rogers, 2005; Adler et al., 2006; McAfoose and Baune, 2009; Hoshiko et al., 2012; Williamson and Bilbo, 2013).”
BackgroundMicroglia‐dependent remodeling of neuronal circuits
Guedes, J. R., Ferreira, P. A., Costa, J. M., Cardoso, A. L., & Peça, J. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15689 · Cited by 93
“However, there was a change in AMPA/NMDA ratio because of an impairment in the normal developmental switch of NMDAR subunits from GluN2B to GluN2A (Hoshiko et al., 2012).”
Background
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
