Cited by 241Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

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How microglia sense and regulate neuronal activity

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Umpierre, Anthony D., Wu, Long‐Jun·2021·Glia

DOI 10.1002/glia.23961PMC PMC8113084

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Abstract

Microglia are innate immune cells of the central nervous system that sense extracellular cues. Brain injuries, inflammation, and pathology evoke dynamic structural responses in microglia, altering their morphology and motility. The dynamic motility of microglia is hypothesized to be a critical first step in sensing local alterations and engaging in pattern-specific responses. Alongside their pathological responses, microglia also sense and regulate neuronal activity. In this review, we consider the extracellular molecules, receptors, and mechanisms that allow microglia to sense neuronal activity changes under both hypoactivity and hyperactivity. We also highlight emerging in vivo evidence that microglia regulate neuronal activity, ranging from physiological to pathophysiological conditions. In addition, we discuss the emerging role of calcium signaling in microglial responses to the extracellular environment. The dynamic function of microglia in monitoring and influencing neuronal activity may be critical for brain homeostasis and circuit modification in health and disease.

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Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,552
Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
Sleep Drives Metabolite Clearance from the Adult Brain
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., et al. (2013) · Science · doi:10.1126/science.1241224 · Cited by 5,411
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
Calcium Signaling
Clapham, D. E. (2007) · Cell · doi:10.1016/j.cell.2007.11.028 · Cited by 4,175
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
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · cited 1×
“In brief, microglia could potentially express the β2 receptor, the β1 receptor, and the α2A receptor based upon transcriptional analysis (Cahoy et al., 2008; Hertz et al., 2010).”
Method
Microglia 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
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus
Parent, J. M., Yu, T. W., Leibowitz, R. T., Geschwind, D. H., Sloviter, R. S., & Lowenstein, D. H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-10-03727.1997 · Cited by 1,872
Resting Microglia Directly Monitor the Functional State of Synapses In Vivo and Determine the Fate of Ischemic Terminals
Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S., & Nabekura, J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4363-08.2009 · Cited by 1,619
Microglial interactions with synapses are modulated by visual experience
Tremblay, M.-È., Lowery, R. L., & Majewska, A. K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000527 · Cited by 1,542
The P2Y12 receptor regulates microglial activation by extracellular nucleotides
Haynes, S. E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M. E., Gan, W.-B., & Julius, D. (2006) · Nature Neuroscience · doi:10.1038/nn1805 · Cited by 1,542
Control 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
Diversity of astrocyte functions and phenotypes in neural circuits
Khakh, B. S., & Sofroniew, M. V. (2015) · Nature Neuroscience · doi:10.1038/nn.4043 · Cited by 1,239
Role for Neuronally Derived Fractalkine in Mediating Interactions between Neurons and CX3CR1-Expressing Microglia
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
Microglial signatures and their role in health and disease
Butovsky, O., & Weiner, H. L. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0057-5 · Cited by 1,046 · cited 1×
“First, P2Y12 is exclusively expressed by microglia in the CNS (Butovsky et al., 2014; Butovsky & Weiner, 2018).”
Background
Negative feedback control of neuronal activity by microglia
Badimon, A., Strasburger, H. J., Ayata, P., Chen, X., Nair, A., Ikegami, A., Hwang, P., Chan, A. T., Graves, S. M., Uweru, J. O., et al. (2020) · Nature · doi:10.1038/s41586-020-2777-8 · Cited by 979
Purinergic signalling in the nervous system: an overview
Abbracchio, M. P., Burnstock, G., Verkhratsky, A., & Zimmermann, H. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.10.001 · Cited by 888
UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis
Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B. V., Jacobson, K. A., Kohsaka, S., & Inoue, K. (2007) · Nature · doi:10.1038/nature05704 · Cited by 802
Aquaporin-4-dependent glymphatic solute transport in the rodent brain
Mestre, H., Hablitz, L. M., Xavier, A. L., Feng, W., Zou, W., Pu, T., Monai, H., Murlidharan, G., Castellanos Rivera, R. M., Simon, M. J., et al. (2018) · eLife · doi:10.7554/elife.40070 · Cited by 738
Circadian control of brain glymphatic and lymphatic fluid flow
Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., Nguyen, R., Benrais, A., & Nedergaard, M. (2020) · Nature Communications · doi:10.1038/s41467-020-18115-2 · Cited by 704
Microglia monitor and protect neuronal function through specialized somatic purinergic junctions
Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A. D., et al. (2020) · Science · doi:10.1126/science.aax6752 · Cited by 684
Hippocampal AstrocytesIn SituRespond to Glutamate Released from Synaptic Terminals
Porter, J. T., & McCarthy, K. D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-16-05073.1996 · Cited by 672
Purinergic signalling and disorders of the central nervous system
Burnstock, G. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2605 · Cited by 662
Sleep promotes branch-specific formation of dendritic spines after learning
Yang, G., Lai, C. S. W., Cichon, J., Ma, L., Li, W., & Gan, W.-B. (2014) · Science · doi:10.1126/science.1249098 · Cited by 616
International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family
Wu, L., Sweet, T.-B., & Clapham, D. E. (2010) · Pharmacological Reviews · doi:10.1124/pr.110.002725 · Cited by 591
Self-citation
Reciprocal Regulation between Resting Microglial Dynamics and Neuronal Activity In Vivo
Li, Y., Du, X.-F., Liu, C., Wen, Z., & Du, J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.10.027 · Cited by 590
Hippocampal Astrocytes In Situ Respond to Glutamate Released from Synaptic Terminals
Porter, J. T., & McCarthy, K. D. (2021) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/s4kv-rg05 · Cited by 561
REM sleep selectively prunes and maintains new synapses in development and learning
Li, W., Ma, L., Yang, G., & Gan, W.-B. (2017) · Nature Neuroscience · doi:10.1038/nn.4479 · Cited by 543
Ca2+ signaling in astrocytes from Ip3r2−/− mice in brain slices and during startle responses in vivo
Srinivasan, R., Huang, B. S., Venugopal, S., Johnston, A. D., Chai, H., Zeng, H., Golshani, P., & Khakh, B. S. (2015) · Nature Neuroscience · doi:10.1038/nn.4001 · Cited by 530
Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex
Sipe, G. O., Lowery, Tremblay, M.-È., Kelly, E. A., Lamantia, C. E., & Majewska, A. K. (2016) · Nature Communications · doi:10.1038/ncomms10905 · Cited by 512
Neuronal Hyperactivity Recruits Microglial Processes via Neuronal NMDA Receptors and Microglial P2Y12 Receptors after Status Epilepticus
Eyo, U. B., Peng, J., Swiatkowski, P., Mukherjee, A., Bispo, A., & Wu, L.-J. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0416-14.2014 · Cited by 509
Self-citation
Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1
Madry, C., Kyrargyri, V., Arancibia-Cárcamo, I. L., Jolivet, R., Kohsaka, S., Bryan, R. M., & Attwell, D. (2018) · Neuron · doi:10.1016/j.neuron.2017.12.002 · Cited by 464
How does adenosine control neuronal dysfunction and neurodegeneration?
Cunha, R. A. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13724 · Cited by 456
Origin of microglia: current concepts and past controversies
Ginhoux, F., & Prinz, M. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020537 · Cited by 446
Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex
Xu, H., Pan, F., Yang, G., & Gan, W. (2007) · Nature Neuroscience · doi:10.1038/nn1883 · Cited by 412
Reducing Astrocyte Calcium Signaling In Vivo Alters Striatal Microcircuits and Causes Repetitive Behavior
Yu, X., Taylor, A. M. W., Nagai, J., Golshani, P., Evans, C. J., Coppola, G., & Khakh, B. S. (2018) · Neuron · doi:10.1016/j.neuron.2018.08.015 · Cited by 407
Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling
Liu, Y., Ying, Y., Li, Y., Eyo, U. B., Chen, T., Zheng, J., Umpierre, A. D., Zhu, J., Bosco, D. B., Dong, H., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0511-3 · Cited by 401
Self-citation
Purine Release, Metabolism, and Signaling in the Inflammatory Response
Linden, J. M., Koch‐Nolte, F., & Dahl, G. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052406 · Cited by 389
Adenosine A2A receptor mediates microglial process retraction
Orr, A. G., Orr, A. L., Traynelis, S. F., Gross, R. E., & Traynelis, S. F. (2009) · Nature Neuroscience · doi:10.1038/nn.2341 · Cited by 361
Characterization of Fractalkine in Rat Brain Cells: Migratory and Activation Signals for CX3CR-1-Expressing Microglia
Maciejewski-Lenoir, D., Chen, S., Feng, L., Maki, R. A., & Bacon, K. B. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1628 · Cited by 361
P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries
André, P., Delaney, S. M., LaRocca, T., Vincent, D., DeGuzman, F. R., Jurek, M., Koller, B., Phillips, D. R., & Conley, P. B. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17864 · Cited by 358
Purine and purinergic receptors
Burnstock, G. (2018) · Brain and Neuroscience Advances · doi:10.1177/2398212818817494 · Cited by 351
Microglia phagocytose myelin sheaths to modify developmental myelination
Hughes, A. N., & Appel, B. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0654-2 · Cited by 344
Vesicular release of ATP at central synapses
Pankratov, Y. V., Lalo, U., Verkhratsky, A., & North, R. A. (2006) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-006-0061-x · Cited by 340
Microglial Morphology and Dynamic Behavior Is Regulated by Ionotropic Glutamatergic and GABAergic Neurotransmission
Fontainhas, A. M., Wang, M., Liang, K. J., Chen, S., Mettu, P., Damani, M., Fariss, R. N., Li, W., & Wong, W. T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015973 · Cited by 334
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
Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex
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
Sensory 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
Novel Hexb-based tools for studying microglia in the CNS
Masuda, T., Amann, L., Sankowski, R., Staszewski, O., Lenz, M., d´Errico, P., Snaidero, N., Costa Jordão, M. J., Böttcher, C., Kierdorf, K., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0707-4 · Cited by 317
Microglia–Neuron Communication in Epilepsy
Eyo, U. B., Murugan, M., & Wu, L. (2016) · Glia · doi:10.1002/glia.23006 · Cited by 300
Self-citation
A Novel Recombinant Plasma Membrane-targeted Luciferase Reveals a New Pathway for ATP Secretion
Pellegatti, P., Falzoni, S., Pinton, P., Rizzuto, R., & Virgilio, F. D. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-03-0222 · Cited by 296
Activation 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
The Elusive P2X7 Macropore
Di Virgilio, F., Schmalzing, G., & Markwardt, F. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.01.005 · Cited by 279
Conditions and Constraints for Astrocyte Calcium Signaling in the Hippocampal Mossy Fiber Pathway
Haustein, M. D., Kracun, S., Lu, X., Shih, T., Jackson‐Weaver, O., Tong, X., Xu, J. P., Yang, X. W., O’Dell, T. J., Marvin, J. S., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.041 · Cited by 266
To Kill a Microglia: A Case for CSF1R Inhibitors
Green, K. N., Crapser, J. D., & Hohsfield, L. A. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.07.001 · Cited by 265
Cortical Circuit Activity Evokes Rapid Astrocyte Calcium Signals on a Similar Timescale to Neurons
Stobart, J. L., Ferrari, K. D., Barrett, M. J. P., Glück, C., Stobart, M. J., Zuend, M., & Weber, B. (2018) · Neuron · doi:10.1016/j.neuron.2018.03.050 · Cited by 254
Adrenoceptors in brain: Cellular gene expression and effects on astrocytic metabolism and [Ca2+]i
Hertz, L., Lovatt, D., Goldman, S. A., & Nedergaard, M. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.03.019 · Cited by 252
Regulation of Dynamic Behavior of Retinal Microglia by CX3CR1 Signaling
Liang, K. J., Lee, J. E., Wang, Y. D., Ma, W., Fontainhas, A. M., Fariss, R. N., & Wong, W. T. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3357 · Cited by 220
Microglia Enhance Synapse Activity to Promote Local Network Synchronization
Akiyoshi, R., Wake, H., Kato, D., Horiuchi, H., Ono, R., Ikegami, A., Haruwaka, K., Omori, T., Tachibana, Y., Moorhouse, A. J., et al. (2018) · eNeuro · doi:10.1523/eneuro.0088-18.2018 · Cited by 218
Microglial calcium signaling is attuned to neuronal activity in awake mice
Umpierre, A. D., Bystrom, L. L., Ying, Y., Liu, Y., Worrell, G. A., & Wu, L. (2020) · eLife · doi:10.7554/elife.56502 · Cited by 214
Self-citation
Nanoscale Surveillance of the Brain by Microglia via cAMP-Regulated Filopodia
Bernier, L.-P., Bohlen, C. J., York, E. M., Choi, H. B., Kamyabi, A., Dissing-Olesen, L., Hefendehl, J. K., Collins, H. Y., Stevens, B., Barres, B. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.010 · Cited by 211
Norepinephrine modulates the motility of resting and activated microglia via different adrenergic receptors
Gyoneva, S., & Traynelis, S. F. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.458901 · Cited by 204
Reorganization of cortical population activity imaged throughout long-term sensory deprivation
Margolis, D. J., Lütcke, H., Schulz, K., Haiss, F., Weber, B., Kügler, S., Hasan, M. T., & Helmchen, F. (2012) · Nature Neuroscience · doi:10.1038/nn.3240 · Cited by 203
Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton
Nolte, C., Möller, T., Walter, T., & Kettenmann, H. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00106-6 · Cited by 199
Functional role of calcium signals for microglial function
Färber, K., & Kettenmann, H. (2006) · Glia · doi:10.1002/glia.20412 · Cited by 198
Neuronal Hyperactivity Disturbs ATP Microgradients, Impairs Microglial Motility, and Reduces Phagocytic Receptor Expression Triggering Apoptosis/Microglial Phagocytosis Uncoupling
Abiega, O., Beccari, S., Díaz‐Aparicio, I., Nadjar, A., Layé, S., Leyrolle, Q., Gómez‐Nicola, D., Domercq, M., Pérez‐Samartín, A., Sánchez-Zafra, V., et al. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002466 · Cited by 190
Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain
Masuda, T., Ozono, Y., Mikuriya, S., Kohro, Y., Tozaki‐Saitoh, H., Iwatsuki, K., Uneyama, H., Ichikawa, R., Salter, M. W., Tsuda, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms12529 · Cited by 182
Ca 2+ Signaling in Cytoskeletal Reorganization, Cell Migration, and Cancer Metastasis
Tsai, F., Kuo, G.-H., Chang, S.-W., & Tsai, P. (2015) · BioMed Research International · doi:10.1155/2015/409245 · Cited by 178
Extracellular ATP activates a cation conductance and a K+ conductance in cultured microglial cells from mouse brain
Walz, W., Ilschner, S., Ohlemeyer, C., Banati, R. B., & Kettenmann, H. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-10-04403.1993 · Cited by 175
Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity
Krabbe, G., Matyash, V., Pannasch, U., Mamer, L., Boddeke, H. W. G. M., & Kettenmann, H. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.12.002 · Cited by 170
P2X4: A fast and sensitive purinergic receptor
Suurväli, J., Boudinot, P., Kanellopoulos, J., & Boudinot, S. R. (2017) · Biomedical Journal · doi:10.1016/j.bj.2017.06.010 · Cited by 169
Dexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs
Lilius, T. O., Blomqvist, K. J., Hauglund, N. L., Liu, G., Stæger, F. F., Bærentzen, S. L., Du, T., Ahlström, F. H. G., Backman, J. T., Kalso, E. A., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.05.005 · Cited by 159
Kainate Seizures Cause Acute Dendritic Injury and Actin Depolymerization In Vivo
Zeng, L.-H., Xu, L., Rensing, N. R., Sinatra, P. M., Rothman, S. M., & Wong, M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0983-07.2007 · Cited by 158
ATP‐induced chemotaxis of microglial processes requires P2Y receptor‐activated initiation of outward potassium currents
Wu, L., Vadakkan, K. I., & Zhuo, M. (2007) · Glia · doi:10.1002/glia.20500 · Cited by 156
Self-citation
Modulation of Microglial Process Convergence Toward Neuronal Dendrites by Extracellular Calcium
Eyo, U. B., Gu, N., De, S., Dong, H., Richardson, J. R., & Wu, L.-J. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3279-14.2015 · Cited by 154
Self-citation
Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion
Chen, T., Lennon, V. A., Liu, Y., Bosco, D. B., Li, Y., Yi, M., Zhu, J., Wei, S., & Wu, L. (2020) · Journal of Clinical Investigation · doi:10.1172/jci134816 · Cited by 149
Self-citation
Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo
Neher, J. J., Neniškytė, U., Hornik, T. C., & Brown, G. C. (2014) · Glia · doi:10.1002/glia.22693 · Cited by 149
Microglial calcium signal acts as a rapid sensor of single neuron damage in vivo
Eichhoff, G., Brawek, B., & Garaschuk, O. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.10.018 · Cited by 148
REM sleep promotes experience-dependent dendritic spine elimination in the mouse cortex
Zhou, Y., Lai, C. S. W., Bai, Y., Li, W., Zhao, R., Yang, G., Frank, M. G., & Gan, W. (2020) · Nature Communications · doi:10.1038/s41467-020-18592-5 · Cited by 139
P2Y12R-Dependent Translocation Mechanisms Gate the Changing Microglial Landscape
Eyo, U. B., Mo, M., Yi, M., Murugan, M., Liu, J., Yarlagadda, R., Margolis, D. J., Xu, P., & Wu, L. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.001 · Cited by 135
Self-citation
Microglial depletion aggravates the severity of acute and chronic seizures in mice
Wu, W., Li, Y., Wei, Y., Bosco, D. B., Xie, M., Zhao, M., Richardson, J. R., & Wu, L. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.028 · Cited by 133
Self-citation
Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice
Peng, J., Liu, Y., Umpierre, A. D., Xie, M., Tian, D., Richardson, J. R., & Wu, L. (2019) · Molecular Brain · doi:10.1186/s13041-019-0492-x · Cited by 132
Self-citation
Microglial Contact Prevents Excess Depolarization and Rescues Neurons from Excitotoxicity
Kato, G., Inada, H., Wake, H., Akiyoshi, R., Miyamoto, A., Eto, K., Ishikawa, T., Moorhouse, A. J., Strassman, A. M., & Nabekura, J. (2016) · eNeuro · doi:10.1523/eneuro.0004-16.2016 · Cited by 128
Activation of mouse microglial cells affects P2 receptor signaling
Möller, T., Kann, O., Verkhratsky, A., & Kettenmann, H. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02244-1 · Cited by 123
Regulation of Physical Microglia–Neuron Interactions by Fractalkine Signaling after Status Epilepticus
Eyo, U. B., Peng, J., Murugan, M., Mo, M., Lalani, A., Xie, P., Xu, P., Margolis, D. J., & Wu, L. (2016) · eNeuro · doi:10.1523/eneuro.0209-16.2016 · Cited by 117
Self-citation
Astrocyte IP3R2-dependent Ca2+ signaling is not a major modulator of neuronal pathways governing behavior
Petravicz, J., Boyt, K. M., & McCarthy, K. D. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00384 · Cited by 116
Bulk Loading of Calcium Indicator Dyes to Study Astrocyte Physiology: Key Limitations and Improvements Using Morphological Maps
Reeves, A. M. B., Shigetomi, E., & Khakh, B. S. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0127-11.2011 · Cited by 115
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 · cited 1×
“However, there are additional mechanisms that also influence microglial motility (Madry & Attwell, 2015).”
Background
In vivo dynamics of innate immune sentinels in the CNS
Nayak, D., Zinselmeyer, B. H., Corps, K. N., & McGavern, D. B. (2012) · IntraVital · doi:10.4161/intv.22823 · Cited by 109
Impairment of in vivo calcium signaling in amyloid plaque-associated microglia
Brawek, B., Schwendele, B., Riester, K., Kohsaka, S., Lerdkrai, C., Liang, Y., & Garaschuk, O. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1242-2 · Cited by 108
Neuronal and glial purinergic receptors functions in neuron development and brain disease
del Puerto, A., Wandosell, F. G., & Garrido, J. J. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00197 · Cited by 106
Microglial P2Y12 Receptor Regulates Seizure-Induced Neurogenesis and Immature Neuronal Projections
Mo, M., Eyo, U. B., Xie, M., Peng, J., Bosco, D. B., Umpierre, A. D., Zhu, X., Tian, D., Xu, P., & Wu, L. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0487-19.2019 · Cited by 95
Self-citation
Intracellular calcium dynamics in cortical microglia responding to focal laser injury in the PC::G5-tdT reporter mouse
Pozner, A., Xu, B., Palumbos, S. D., Gee, J. M., Tvrdík, P., & Capecchi, M. R. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00012 · Cited by 94
How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?
Gasperini, R., Pavez, M., Thompson, A. C., Mitchell, C. B., Hardy, H., Young, K. M., Chilton, J. K., & Foa, L. C. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.07.006 · Cited by 88
The adenosine generating enzymes CD39/CD73 control microglial processes ramification in the mouse brain
Matyash, M., Zabiegalov, O., Wendt, S., Matyash, V., & Kettenmann, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175012 · Cited by 86
Resting Microglial Motility Is Independent of Synaptic Plasticity in Mammalian Brain
Wu, L., & Zhuo, M. (2008) · Journal of Neurophysiology · doi:10.1152/jn.01210.2007 · Cited by 81
Self-citation
Role of norepinephrine in the regulation of rapid eye movement sleep
Mallick, B. N., Majumdar, S., Faisal, M., Yadav, V., Madan, V., & Pal, D. (2002) · Journal of Biosciences · doi:10.1007/bf02705052 · Cited by 80
Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines
Pfeiffer, T., Avignone, E., & Nägerl, U. V. (2016) · Scientific Reports · doi:10.1038/srep32422 · Cited by 79
The mysterious origins of microglia
Ginhoux, F., & Garel, S. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0176-3 · Cited by 78
Altered Expression of CX3CL1 in Patients with Epilepsy and in a Rat Model
Xu, Y., Zeng, K., Han, Y., Wang, L., Chen, D., Xi, Z., Wang, H., Wang, X., & Chen, G. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.01.024 · Cited by 77
Activation of microglial P2Y12 receptor is required for outward potassium currents in response to neuronal injury
Swiatkowski, P., Murugan, M., Eyo, U. B., Wāng, Y., Rangaraju, S., Oh, S. B., & Wu, L. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.01.008 · Cited by 75
Self-citation
P2X7 receptor activation regulates microglial cell death during oxygen-glucose deprivation
Eyo, U. B., Miner, S. A., Ahlers‐Dannen, K. E., Wu, L., & Dailey, M. E. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.032 · Cited by 75
Self-citation
Transcranial Direct Current Stimulation (tDCS) Induces Adrenergic Receptor-Dependent Microglial Morphological Changes in Mice
Mishima, T., Nagai, T., Yahagi, K., Akther, S., Oe, Y., Monai, H., Kohsaka, S., & Hirase, H. (2019) · eNeuro · doi:10.1523/eneuro.0204-19.2019 · Cited by 70
Microglial Displacement of GABAergic Synapses Is a Protective Event during Complex Febrile Seizures
Wan, Y., Feng, B., You, Y., Yu, J., Xu, C., Dai, H., Trapp, B. D., Shi, P. D., Chen, Z., & Hu, W. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108346 · Cited by 70
P2Y13 receptors regulate microglial morphology, surveillance, and resting levels of interleukin 1β release
Kyrargyri, V., Madry, C., Rifat, A., Arancibia‐Cárcamo, I. L., Jones, S. P., Chan, V. T. T., Xu, Y., Robaye, B., & Attwell, D. (2019) · Glia · doi:10.1002/glia.23719 · Cited by 69
Selective Activation of KCa3.1 and CRAC Channels by P2Y2 Receptors Promotes Ca2+ Signaling, Store Refilling and Migration of Rat Microglial Cells
Ferreira, R., & Schlichter, L. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062345 · Cited by 66
Healthy Brain Aging Modifies Microglial Calcium Signaling In Vivo
Olmedillas, M., Asavapanumas, N., Uzcategui, N. L., & Garaschuk, O. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030589 · Cited by 60
In vivo characterization of functional states of cortical microglia during peripheral inflammation
Riester, K., Brawek, B., Savitska, D., Fröhlich, N. T., Zirdum, E., Mojtahedi, N., Heneka, M. T., & Garaschuk, O. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.12.007 · Cited by 60
Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion
Madry, C., Arancibia‐Cárcamo, I. L., Kyrargyri, V., Chan, V. T. T., Hamilton, N. B., & Attwell, D. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715354115 · Cited by 58
The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron Physical Interactions
Eyo, U. B., Bispo, A., Liu, J., Sabu, S., Wu, R., DiBona, V. L., Zheng, J., Murugan, M., Zhang, H., Tang, Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-19205-4 · Cited by 57
Self-citation
Brain microdialysate monoamines in relation to circadian rhythms, sleep, and sleep deprivation - a systematic review, network meta-analysis, and new primary data
Menon, J. M. L., Nolten, C., Achterberg, E. J. M., Joosten, R. N. J. M. A., Dematteis, M., Feenstra, M. G. P., Drinkenburg, W. H. (., & Leenaars, C. H. C. (2019) · Journal of Circadian Rhythms · doi:10.5334/jcr.174 · Cited by 57
Complement factor C5a and epidermal growth factor trigger the activation of outward potassium currents in cultured murine microglia
Ilschner, S., Nolte, C., & Kettenmann, H. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00107-8 · Cited by 54
Biophysical basis for Kv1.3 regulation of membrane potential changes induced by P2X4 ‐mediated calcium entry in microglia
Nguyen, H. M., Lucente, J. D., Chen, Y., Cui, Y., Ibrahim, R. H., Pennington, M. W., Jin, L., Maezawa, I., & Wulff, H. (2020) · Glia · doi:10.1002/glia.23847 · Cited by 54
In vivo imaging of dendritic spines during electrographic seizures
Rensing, N. R., Ouyang, Y., Yang, X., Yamada, K. A., Rothman, S. M., & Wong, M. L. (2005) · Annals of Neurology · doi:10.1002/ana.20658 · Cited by 51
Imaging P2X4 Receptor Lateral Mobility in Microglia
Toulmé, E., & Khakh, B. S. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.329334 · Cited by 47
Effect of Caloric Restriction on the in vivo Functional Properties of Aging Microglia
Olmedillas, M., Fröhlich, N. T., Figarella, K., Mojtahedi, N., & Garaschuk, O. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00750 · Cited by 46
CCL5 evokes calcium signals in microglia through a kinase‐, phosphoinositide‐, and nucleotide‐dependent mechanism
Shideman, C. R., Hu, S., Peterson, P. K., & Thayer, S. A. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20839 · Cited by 45
Neuroprotective effects of microglial P2Y 1 receptors against ischemic neuronal injury
Fukumoto, Y., Tanaka, K. F., Parajuli, B., Shibata, K., Yoshioka, H., Kanemaru, K., Gachet, C., Ikenaka, K., Koizumi, S., & Kinouchi, H. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18805317 · Cited by 45
Spontaneous Ca2+ transients in mouse microglia
Korvers, L., Costa, A. D. A., Mersch, M., Matyash, V., Kettenmann, H., & Semtner, M. (2016) · Cell Calcium · doi:10.1016/j.ceca.2016.09.004 · Cited by 44
Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia
Jiang, P., Xing, F., Guo, B., Yang, J., Li, Z., Wei, W., Hu, F. Z., Lee, I., Zhang, X., Pan, L., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183114 · Cited by 42
New P2Y12blockers
Cattaneo, M. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03382.x · Cited by 42
Resting microglia respond to and regulate neuronal activity in vivo
Li, Y., Du, X.-F., & Du, J. (2013) · Communicative & Integrative Biology · doi:10.4161/cib.24493 · Cited by 39
Cholinergic agonists increase intracellular Ca2+ in cultured human microglia
Zhang, L., McLarnon, J. G., Goghari, V., Lee, Y. B., Kim, S. U., & Krieger, C. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00706-x · Cited by 36
Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling
Doolen, S., Cook, J., Riedl, M. S., Kitto, K. F., Kohsaka, S., Honda, C. N., Fairbanks, C. A., Taylor, B. K., & Vulchanova, L. (2017) · Glia · doi:10.1002/glia.23208 · Cited by 35
Regulation of microglia by neuromodulators: Modulations in major and minor modes
Albertini, G., Etienne, F., & Roumier, A. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135000 · Cited by 35
Extracellular acidosis impairs P2Y receptor-mediated Ca2+ signalling and migration of microglia
Langfelder, A., Okonji, P. E., Deca, D., Wei, W., & Glitsch, M. D. (2015) · Cell Calcium · doi:10.1016/j.ceca.2015.01.004 · Cited by 28
Regulation of the Plasma Membrane Calcium ATPases by the actin cytoskeleton
Dalghi, M. G., Ferreira-Gomes, M., & Rossi, J. P. F. C. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.11.151 · Cited by 26
Augmentation of Ca2+ signaling in astrocytic endfeet in the latent phase of temporal lobe epilepsy
Szokol, K., Heuser, K., Tang, W., Jensen, V., Enger, R., Bedner, P., Steinhäuser, C., TaubÃ¸ll, E., Ottersen, O. P., & Nagelhus, E. A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00049 · Cited by 23
Donepezil suppresses intracellular Ca2+ mobilization through the PI3K pathway in rodent microglia
Haraguchi, Y., Mizoguchi, Y., Ohgidani, M., Imamura, Y., Murakawa‐Hirachi, T., Nabeta, H., Tateishi, H., Kato, T. A., & Monji, A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1033-0 · Cited by 22
Phosphoinositide 3-kinase γ ties chemoattractant- and adrenergic control of microglial motility
Schneble, N., Schmidt, C., Bauer, R., Müller, J. P., Monajembashi, S., & Wetzker, R. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.11.002 · Cited by 19
Microglia in Neuronal Circuits
Wu, L., Stevens, B., Duan, S., & MacVicar, B. A. (2013) · Neural Plasticity · doi:10.1155/2013/586426 · Cited by 19
Self-citation
IP3-Mediated Calcium Signaling Is Involved in the Mechanism of Fractalkine-Induced Hyperalgesia Response
Wang, A., Yang, T., Zhang, L., Jia, L., Wu, Q., Yao, S., Xu, J., & Yang, H. (2018) · Medical Science Monitor · doi:10.12659/msm.913787 · Cited by 14

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Authors: Umpierre, A. D., & Wu, L.
Affiliations: Mayo Clinic (US)
Corresponding author: Wu, Long‐Jun
ORCID: Umpierre, Anthony D.
Wu, Long‐Jun
Venue: Glia
Publisher: Wiley
Published: 2020-12-28
Volume: 69
Issue: 7
Pages: 1637-1653
ISSN: 0894-1491 (ISSN-L)
1098-1136
DOI: 10.1002/glia.23961
PMC: PMC8113084
OpenAlex: W3115061260
Cited by: 237
References: 137
Citations by year: 2026: 36 · 2025: 62 · 2024: 52 · 2023: 44 · 2022: 28 · 2021: 14
FWCI: 2.24
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Glia (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (NS088627, NS110825, NS110949, NS112144, NS114040)
National Institute on Aging (AG064159)
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: microglia, microglial motility, microglial morphology, microglial receptors, calcium signaling, neuronal hyperactivity, brain homeostasis, neuroinflammation, circuit modification
MeSH terms: Brain, Central Nervous System, Neurons, Microglia, Calcium Signaling

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