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Cited by 512Neuroinflammation and Neurodegeneration MechanismsNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex

Open access
Sipe, G. O., Lowery,, R. L., Tremblay, M-È, Kelly, E. A., Lamantia, C. E., Majewska, A. K.·2016·Nature Communications
DOI 10.1038/ncomms10905PMC PMC4786684
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Abstract

Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, particularly during early development. Here we demonstrate that microglia are critical for ocular dominance plasticity. During the visual critical period, closure of one eye elicits changes in the structure and function of connections underlying binocular responses of neurons in the visual cortex. We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity. These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain.

AI snapshot

Written from the paper’s full text.

TL;DR

Microglia rapidly alter morphology, motility, and synapse interactions during monocular deprivation in mouse visual cortex, and disrupting microglial P2Y12 signaling blocks ocular dominance plasticity. These findings identify P2Y12-dependent microglial responses as necessary for experience-dependent synaptic plasticity.

Key findings

  • During monocular deprivation (MD) in the visual critical period, microglia in contralateral binocular visual cortex became hyper-ramified after 12 h and remained so until 4 days MD, returning near basal by 7 days; hyper-ramification was limited to contralateral binocular visual cortex and was not accompanied by changes in soma area, Iba-1 intensity, MHC-II, or CD45.
  • In vivo two-photon imaging showed no change in microglial density at 2 or 4 days MD, but reduced process motility in deprived animals after 2 or 4 days (two-way ANOVA, P<0.01).
  • Electron microscopy showed MD significantly increased microglial contacts with synaptic clefts (P<0.05) and processes with inclusions (P<0.05), with the highest number of inclusions at 2-day MD; GluA1 puncta within microglial cytoplasm increased after deprivation (Student’s t-test, P<0.0001).
  • Disrupting P2Y12 with clopidogrel or P2Y12 knockout prevented the ocular dominance shift after 4 days MD (P>0.05), whereas saline controls shifted (P<0.001); ticagrelor, which does not cross the blood–brain barrier, did not block the shift (P<0.05). P2Y12KO mice also lacked the MD-induced decrease in motility and MD-induced increases in synaptic cleft contacts, inclusions, and GluA1 puncta.

Methods

  • Mice on a C57/Bl6 background were studied during the visual critical period (P25–35); monocular deprivation was performed at P28±1, and analyses were contralateral to the deprived eye unless stated otherwise, with experiments and analyses blind to genotype and manipulation.
  • Approaches included fixed histology with confocal Sholl analysis, in vivo two-photon microscopy in CX3CR1-GFP and P2Y12KO crosses, electron microscopy, immunohistochemistry for GluA1, and intrinsic optical signal imaging to calculate an ocular dominance index; pharmacology used clopidogrel (50 mg kg−1, i.p.) and ticagrelor (10 mg kg−1, i.p.).
  • Statistics used two-tailed unpaired Student’s t-tests and one-way or two-way ANOVAs with Holm-Sidak post hoc comparisons; n-values represent individual animals, and α=0.05.

Limitations

  • The paper states that electron microscopy used single ultrathin sections without serial sectioning or three-dimensional reconstruction, so inclusions cannot be confirmed as true engulfment rather than partial wrapping of microglial processes around other brain elements.
  • The paper states that analysis of microglial motility, phagocytosis, and synaptic contact was restricted to cortical layers 1 and 2; additional roles in infragranular and granular layers may occur at slower timescales following MD.
  • The paper states it does not address the processes leading to ATP release, downstream signaling in microglia, or the mechanism mediating microglial actions at synapses. Evident from the text: several experiments used small group sizes (e.g., n=3–6 per group), which may limit statistical power; this is not stated as a limitation by the authors.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/ncomms10905

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 31 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Microglia respond to monocular deprivation during the critical period by altering their morphology, motility, phagocytic behaviour, and interactions with synapses.

    “We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses.”
    Quote in the paperSubstantial claim
  • Findingnone given

    Hyper-ramification also occurs in P2Y12KO microglia.

    “because hyper-ramification also occurs in P2Y12KO microglia”
    Quote in the paperSubstantial claim
  • Findingown data

    The density of GluA1 puncta within microglial cytoplasm significantly increased after deprivation.

    “A quantification demonstrated a significant increase in GluA1 puncta within the microglial cytoplasm after deprivation (Fig. 3g; Student's t-test; P<0.0001), demonstrating active engulfment of synaptic material by microglia during periods of ODP.”
    Quote in the paperSubstantial claim
  • Findingown data

    Microglial process motility was reduced in deprived animals after 2 or 4 days of monocular deprivation.

    “However, we found a significant change in microglial process motility after deprivation. While microglia displayed high levels of both extension and retraction on the first day of imaging in both control and experimental groups before deprivation was initiated, re-imaging after 2 or 4 days showed a reduction in the motility of microglial processes in the deprived animals only (Fig. 2d;”
    Quote in the paperSubstantial claim
  • Findingown data

    Blocking P2Y12 peripherally with ticagrelor does not affect plasticity.

    “Our experiments using a P2Y12 inhibitor that does not cross the BBB—ticagrelor—demonstrate that blocking P2Y12 peripherally does not affect plasticity.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Ticagrelor does not cross the blood-brain barrier.
  • May combine two claims. 8
  • Classified as probably not a substantial claim. 24

  • May combine two claims.

    Findingown data

    The number of microglial contacts with synaptic clefts was significantly increased by monocular deprivation and remained elevated throughout the deprivation period up to 7 days.

    “The number of microglial contacts with synaptic clefts, however, was significantly increased by MD (Fig. 3c, one-way ANOVA, P<0.05) and remained elevated throughout the deprivation period (up to 7 days).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The number of processes with inclusions was significantly elevated following deprivation, with the highest number observed at 2-day monocular deprivation.

    “However, the number of processes with such inclusions was significantly elevated following deprivation (Fig. 3d, one-way ANOVA, P<0.05), with the highest number of inclusions observed at 2-day MD, supporting an early role for microglia in ODP during the pruning of connections from the deprived eye.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Microglia react rapidly to changes in cortical activity, increasing process arborization, reducing process motility, and increasing interactions with synaptic elements.

    “Here we demonstrate that microglia react rapidly to changes in cortical activity, increasing process arborization, reducing process motility and increasing their interactions with synaptic elements.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    For both sets of motility experiments, no trends towards increased or decreased motility were observed when comparing the first three imaging time points to the last three imaging time points.

    “For both sets of motility experiments, we did not observe trends towards increased or decreased motility when comparing the first three imaging time points to the last three imaging time points.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Microglia dynamically interact with neuronal circuits, making direct contacts with synaptic elements in a way modulated by experience-dependent changes in neuronal activity.

    “Microglia dynamically interact with neuronal circuits, making direct contacts with synaptic elements1819 in a way that is modulated by experience-dependent changes in neuronal activity19.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S. & Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29, 3974–3980 (2009). source

      Not checked in the free run.

    • cites [19] Tremblay, M. E., Lowery, R. L. & Majewska, A. K. Microglial interactions with synapses are modulated by visual experience. PLoS Biol. 8, e1000527 (2010). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Activation of the Gi/o-coupled purinergic receptor P2Y12 powerfully alters microglial dynamics in vivo.

    “The microglial expression of most of these receptors has been demonstrated in vitro, but activation of the Gi/o-coupled purinergic receptor, P2Y12, has been shown to powerfully alter microglial dynamics in vivo21.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All experiments and analyses were carried out blind to genotype and manipulation.

    “All experiments and analyses were carried out blind to genotype and manipulation.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    P2Y12 signalling would result in the targeting of microglial processes to synaptic elements requiring elimination.

    “Thus, P2Y12 signalling would result in the targeting of microglial processes to synaptic elements requiring elimination, at which point other pathways including those mediating phagocytosis could become active.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microglia can potentiate NMDA receptor activity through glycine release.

    “Microglia can also potentiate NMDA receptor activity through glycine release54”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Hayashi, Y., Ishibashi, H., Hashimoto, K. & Nakanishi, H. Potentiation of the NMDA receptor-mediated responses through the activation of the glycine site by microglia secreting soluble factors. Glia 53, 660–668 (2006). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microglia actively shape maturing neuronal networks within the first few weeks of life in the mouse via the complement and fractalkine systems.

    “For example, microglia actively shape maturing neuronal networks within the first few weeks of life in the mouse via the complement and fractalkine systems45.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691–705 (2012). source

      Not checked in the free run.

    • cites [5] Zhan, Y. et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17, 400–406 (2014). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    P2Y12 elicits rapid and pronounced chemotactic responses of microglial processes.

    “P2Y12 is highly sensitive to adenosine diphosphate, abundantly and selectively expressed in homeostatic microglia, rapidly downregulated following the initiation of inflammation and elicits rapid and pronounced chemotactic responses of microglial processes2122.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source

      Not checked in the free run.

    • cites [22] Honda, S. et al. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J.Neurosci. 21, 1975–1982 (2001). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The vasculature was labelled with retro-orbital injection of 4% tetramethylrhodamine dextran in saline to ensure that the blood-brain barrier was not compromised by laser injury.

    “The vasculature was labelled using a retro-orbital injection of 4% tetramethylrhodamine dextran in saline to ensure that the BBBwas not compromised by laser injury.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The initial hyper-ramification does not target microglial processes to synapses but instead serves as an initial alert, allowing microglia to adopt a state that aids in their subsequent actions at synapses.

    “This suggests that the initial hyper-ramification does not target microglial processes to synapses but instead serves as an initial alert, allowing microglia to adopt a state that aids in their subsequent actions at synapses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Microglia in the healthy brain are highly motile and actively survey the brain parenchyma.

    “However, landmark studies demonstrated that microglia in the healthy brain are highly motile, actively surveying the brain parenchyma23.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Davalos, D. et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8, 752–758 (2005). source

      Not checked in the free run.

    • cites [3] Nimmerjahn, A., Kirchhoff, F. & Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314–1318 (2005). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    All n-values represent individual animals and are comparable to standard n values used in similar experiments in the literature.

    “All n-values represent individual animals, and are comparable to standard n values used in similar experiments in the literature.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Once microglia have been alerted through another mechanism, P2Y12 signalling may be involved in the extension of processes specifically towards synapses undergoing LTD.

    “Once microglia have been alerted through another mechanism, P2Y12 signalling may then be involved in the extension of processes specifically towards synapses undergoing LTD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    P2Y12 is rapidly downregulated following initiation of inflammation.

    “P2Y12 is highly sensitive to adenosine diphosphate, abundantly and selectively expressed in homeostatic microglia, rapidly downregulated following the initiation of inflammation and elicits rapid and pronounced chemotactic responses of microglial processes2122.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source

      Not checked in the free run.

    • cites [22] Honda, S. et al. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J.Neurosci. 21, 1975–1982 (2001). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    P2Y12 mediates process motility during early injury responses.

    “we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source

      Not checked in the free run.

    • cites [22] Honda, S. et al. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J.Neurosci. 21, 1975–1982 (2001). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    P2Y12 is highly sensitive to adenosine diphosphate.

    “P2Y12 is highly sensitive to adenosine diphosphate, abundantly and selectively expressed in homeostatic microglia, rapidly downregulated following the initiation of inflammation and elicits rapid and pronounced chemotactic responses of microglial processes2122.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source

      Not checked in the free run.

    • cites [22] Honda, S. et al. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J.Neurosci. 21, 1975–1982 (2001). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microglia can promote LTD via NADPH oxidase.

    “and promote LTD via NADPH oxidase55”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Zhang, J. et al. Microglial CR3 activation triggers long-term synaptic depression in the hippocampus via NADPH oxidase. Neuron 82, 195–207 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Microglial behaviour during periods of plasticity is reminiscent of changes observed during pathology, but the pathways used are distinct from traditional activation.

    “This suggests that, while microglial behaviour during periods of plasticity is reminiscent of changes observed during pathology, the pathways used are distinct from traditional activation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microglia respond to changes in ionotropic neurotransmission via the intermediary release of ATP by astrocytes.

    “and that microglia respond to changes in ionotropic neurotransmission via the intermediary release of ATP by astrocytes20.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Fontainhas, A. M. et al. Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PLoS ONE 6, e15973 (2011). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The first phase of ODP requires NMDA receptor-dependent long-term depression (LTD).

    “Interestingly, the first phase of ODP requires NMDA receptor-dependent long-term depression (LTD)52.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Bear, M. F., Kleinschmidt, A., Gu, Q. A. & Singer, W. Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist. J. Neurosci. 10, 909–925 (1990). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Measurements were normalized to the area of individual microglial processes to account for the fact that large processes can interact with more brain elements and contain more inclusions than smaller processes.

    “For quantification, measurements were normalized to the area of individual microglial processes to account for the fact that large processes have the ability to interact with more brain elements and contain more inclusions than smaller processes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Astrocyte-microglia communication dictates which synaptic elements should be pruned during thalamo-cortical network refinement.

    “evidence suggesting that astrocyte–microglia communication dictates which synaptic elements should be pruned during thalamo–cortical network refinement,56”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Bialas, A. R. & Stevens, B. TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat. Neurosci. 16, 1773–1782 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    For accurate, objective thresholding, the triangle method of auto-thresholding was selected.

    “For accurate, objective thresholding, the triangle method of auto-thesholding was selected58.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] Zack, G. W., Rogers, W. E. & Latt, S. A. Automatic measurement of sister chromatid exchange frequency. J. Histochem. Cytochem. 25, 741–753 (1977). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    P2Y12 expression correlates strongly with ramified microglial morphology characteristic of healthy neurophysiology.

    “In addition, its expression correlates strongly with a ramified microglial morphology characteristic of healthy neurophysiology, indicating that it primarily functions during rapid responses to perturbations of brain homeostasis2123.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Haynes, S. E. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). source

      Not checked in the free run.

    • cites [23] Butovsky, O. et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Because animals had been anaesthetized using avertin, time-lapse imaging was not stable enough to allow for a more automated analysis of motility.

    “Because these animals had been anaesthetized using avertin, time-lapse imaging was not stable enough to allow for a more automated analysis of motility (see below).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Neuronal NMDA receptor stimulation can provoke local neuronal ATP release sufficient to induce transient microglial process extension via P2Y12.

    “Recent work has suggested that neuronal N-methyl-D-aspartate (NMDA) receptor stimulation can provoke local neuronal ATP release that is sufficient to induce transient microglial process extension via P2Y12 (refs 495049,50).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [49] Dissing-Olesen, L. et al. Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J. Neurosci. 34, 10511–10527 (2014). source

      Not checked in the free run.

    • cites [50] Eyo, U. B. et al. Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. J. Neurosci. 34, 10528–10540 (2014). source

      Not checked in the free run.

29 of 29

  • The paper relies on this without support.

    Microglial contributions to network maintenance and plasticity at later developmental stages and the underlying mechanisms remain poorly understood.

    “However, microglial contributions to network maintenance and plasticity at later developmental stages and the underlying mechanisms remain poorly understood.”

  • The paper relies on this without support.

    Microglial involvement in ocular dominance plasticity has remained unknown.

    “However, microglial involvement in ODP has remained unknown.”

  • The paper relies on this without support.

    The signalling pathways regulating microglial interactions with neuronal circuits are not well understood.

    “While the signalling pathways regulating these interactions are not well understood, there are a number of receptors expressed by microglia that can convey information regarding changes in normal brain homeostasis120.”

  • The paper relies on this without support.

    At 12 h after eye closure, neuronal synapses have not yet undergone plastic changes and ocular dominance in cortical neurons within binocular visual cortex has not been altered.

    “We observed hyper-ramification within 12 h after eye closure, a time point at which neuronal synapses have not yet undergone plastic changes and ocular dominance in cortical neurons within bV1 has not been altered.”

  • The paper relies on this without support.

    Ticagrelor does not cross the blood-brain barrier.

    “Our experiments using a P2Y12 inhibitor that does not cross the BBB—ticagrelor—demonstrate that blocking P2Y12 peripherally does not affect plasticity.”
5 of 5

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?

  • Mice lacking microglia P2Y12 receptors show deficits in early monocular deprivation-associated visual cortical plasticity.

    “Microglia are also likely to be required for environment-induced brain plasticity as mice lacking microglia P2Y12 receptors show deficits in early monocular deprivation-associated visual cortical plasticity14.”

    From Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction (2018) · cites this paper as [14]

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. Haynes, S. E. et al. The P2Y(12) receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9, 1512–1519 (2006). · DOI · Paper page

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Related

Authors
Sipe, G. O., Lowery, Tremblay, M.-È., Kelly, E. A., Lamantia, C. E., & Majewska, A. K.
Affiliations
University of Rochester Medicine (US)
Corresponding author
Majewska, A. K.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-03-07
Volume
7
Issue
1
Pages
10905-10905
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms10905
PMC
PMC4786684
OpenAlex
W2296597812
Semantic Scholar
c4565f14c58891ada54c925caf6ad31f949be259
Cited by
512
References
62
Citations by year
2026: 28 · 2025: 40 · 2024: 74 · 2023: 59 · 2022: 68 · 2021: 64 · 2020: 46 · 2019: 42 · 2018: 39 · 2017: 37 · 2016: 15
FWCI
24.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • Medical Center, University of Rochester
  • National Eye Institute (R01EY013319, R01EY019277, EY019277, EY013319)
  • National Institute of Neurological Disorders and Stroke (F31NS086241, T32NS007489)
  • National Institute of Environmental Health Sciences (T32 ES 7026-34, T32ES007026)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
microglia, P2Y12 receptor, ocular dominance plasticity, visual cortex, monocular deprivation, synaptic plasticity, microglial motility, phagocytosis, experience-dependent plasticity, binocular vision
MeSH terms
Animals, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Synapses, Visual Cortex, Microglia, Dominance, Ocular, Mice, Receptors, Purinergic P2Y12

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