1932

Abstract

Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning of these cells, the number, morphology, and function of synaptic contacts are profoundly altered, resulting in abnormal connectivity and behavioral abnormalities. In addition to their role in synaptic refinement, glial cells have also been implicated in pathological synapse loss and dysfunction following injury or nervous system degeneration in adults. Although mechanisms regulating glia-mediated synaptic elimination are still being uncovered, it is clear this complex process involves many cues that promote and inhibit the removal of specific synaptic connections. Gaining a greater understanding of these signals and the contribution of different cell types will not only provide insight into this critical biological event but also be instrumental in advancing knowledge of brain development and neural disease.

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2019-07-08
2024-10-08
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Literature Cited

  1. Allen NJ. 2014. Astrocyte regulation of synaptic behavior. Annu. Rev. Cell Dev. Biol. 30:439–63
    [Google Scholar]
  2. Allen NJ, Eroglu C. 2017. Cell biology of astrocyte-synapse interactions. Neuron 96:697–708
    [Google Scholar]
  3. Altman J. 1972. Postnatal development of the cerebellar cortex in the rat. II. Phases in the maturation of Purkinje cells and of the molecular layer. J. Comp. Neurol. 145:399–463
    [Google Scholar]
  4. Armati PJ, Mathey EK. 2013. An update on Schwann cell biology—immunomodulation, neural regulation and other surprises. J. Neurol. Sci. 333:68–72
    [Google Scholar]
  5. Awasaki T, Ito K. 2004. Engulfing action of glial cells is required for programmed axon pruning during Drosophila metamorphosis. Curr. Biol. 14:668–77
    [Google Scholar]
  6. Awasaki T, Tatsumi R, Takahashi K, Arai K, Nakanishi Y et al. 2006. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis. Neuron 50:855–67
    [Google Scholar]
  7. Bagri A, Cheng HJ, Yaron A, Pleasure SJ, Tessier-Lavigne M 2003. Stereotyped pruning of long hippocampal axon branches triggered by retraction inducers of the semaphorin family. Cell 113:285–99
    [Google Scholar]
  8. Bahrini I, Song JH, Diez D, Hanayama R 2015. Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors in microglia. Sci. Rep. 5:7989
    [Google Scholar]
  9. Balice-Gordon RJ, Lichtman JW. 1994. Long-term synapse loss induced by focal blockade of postsynaptic receptors. Nature 372:519–24
    [Google Scholar]
  10. Barber MJ, Lichtman JW. 1999. Activity-driven synapse elimination leads paradoxically to domination by inactive neurons. J. Neurosci. 19:9975–85
    [Google Scholar]
  11. Bjorkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R et al. 2008. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J. Exp. Med. 205:1869–77
    [Google Scholar]
  12. Bolam JP, Pissadaki EK. 2012. Living on the edge with too many mouths to feed: why dopamine neurons die. Mov. Disord. 27:1478–83
    [Google Scholar]
  13. Borroni B, Ferrari F, Galimberti D, Nacmias B, Barone C et al. 2014. Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging 35:934e7–e10
    [Google Scholar]
  14. Buffelli M, Burgess RW, Feng G, Lobe CG, Lichtman JW, Sanes JR 2003. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424:430–34
    [Google Scholar]
  15. Busetto G, Buffelli M, Tognana E, Bellico F, Cangiano A 2000. Hebbian mechanisms revealed by electrical stimulation at developing rat neuromuscular junctions. J. Neurosci. 20:685–95
    [Google Scholar]
  16. Butts DA, Kanold PO, Shatz CJ 2007. A burst-based “Hebbian” learning rule at retinogeniculate synapses links retinal waves to activity-dependent refinement. PLOS Biol 5:e61
    [Google Scholar]
  17. Cady J, Koval ED, Benitez BA, Zaidman C et al. 2014. TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol 71:449–53
    [Google Scholar]
  18. Cang J, Wang L, Stryker MP, Feldheim DA 2008. Roles of ephrin-As and structured activity in the development of functional maps in the superior colliculus. J. Neurosci. 28:11015–23
    [Google Scholar]
  19. Chedotal A, Sotelo C. 1992. Early development of olivocerebellar projections in the fetal rat using CGRP immunocytochemistry. Eur. J. Neurosci. 4:1159–79
    [Google Scholar]
  20. Chen SK, Tvrdik P, Peden E, Cho S, Wu S et al. 2010. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell 141:775–85
    [Google Scholar]
  21. Cherra SJ 3rd, Jin Y 2016. A two-immunoglobulin-domain transmembrane protein mediates an epidermal-neuronal interaction to maintain synapse density. Neuron 89:325–36
    [Google Scholar]
  22. Chu Y, Jin X, Parada I, Pesic A, Stevens B et al. 2010. Enhanced synaptic connectivity and epilepsy in C1q knockout mice. PNAS 107:7975–80
    [Google Scholar]
  23. Chung WS, Barres BA. 2012. The role of glial cells in synapse elimination. Curr. Opin. Neurobiol. 22:438–45
    [Google Scholar]
  24. Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A et al. 2013. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504:394–400
    [Google Scholar]
  25. Chung WS, Welsh CA, Barres BA, Stevens B 2015. Do glia drive synaptic and cognitive impairment in disease?. Nat. Neurosci. 18:1539–45
    [Google Scholar]
  26. Colman H, Lichtman JW. 1993. Interactions between nerve and muscle: synapse elimination at the developing neuromuscular junction. Dev. Biol. 156:1–10
    [Google Scholar]
  27. Darabid H, Arbour D, Robitaille R 2013. Glial cells decipher synaptic competition at the mammalian neuromuscular junction. J. Neurosci. 33:1297–313
    [Google Scholar]
  28. Dejanovic B, Huntley MA, Mazière AD, Meilandt WJ, Wu T et al. 2018. Changes in the synaptic proteome in tauopathy and rescue of tau-induced synapse loss by C1q antibodies. Neuron 100:1322–36.e7
    [Google Scholar]
  29. DeKosky ST, Scheff SW. 1990. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann. Neurol. 27:457–64
    [Google Scholar]
  30. Dichter GS. 2012. Functional magnetic resonance imaging of autism spectrum disorders. Dialogues Clin. Neurosci. 14:319–51
    [Google Scholar]
  31. Dinstein I, Pierce K, Eyler L, Solso S, Malach R et al. 2011. Disrupted neural synchronization in toddlers with autism. Neuron 70:1218–25
    [Google Scholar]
  32. Dissing-Olesen L, LeDue JM, Rungta RL, Hefendehl JK, Choi HB, MacVicar BA 2014. Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J. Neurosci. 34:10511–27
    [Google Scholar]
  33. Doherty J, Logan MA, Tasdemir OE, Freeman MR 2009. Ensheathing glia function as phagocytes in the adult Drosophila brain. J. Neurosci. 29:4768–81
    [Google Scholar]
  34. Doretto S, Malerba M, Ramos M, Ikrar T, Kinoshita C et al. 2011. Oligodendrocytes as regulators of neuronal networks during early postnatal development. PLOS ONE 6:e19849
    [Google Scholar]
  35. Doty KR, Guillot-Sestier MV, Town T 2015. The role of the immune system in neurodegenerative disorders: adaptive or maladaptive?. Brain Res 1617:155–73
    [Google Scholar]
  36. Eilam R, Pinkas-Kramarski R, Ratzkin BJ, Segal M, Yarden Y 1998. Activity-dependent regulation of Neu differentiation factor/neuregulin expression in rat brain. PNAS 95:1888–93
    [Google Scholar]
  37. Elward K, Gasque P. 2003. “Eat me” and “don't eat me” signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol. Immunol. 40:85–94
    [Google Scholar]
  38. Estes ML, McAllister AK. 2015. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat. Rev. Neurosci. 16:469–86
    [Google Scholar]
  39. Estes ML, McAllister AK. 2016. Maternal immune activation: implications for neuropsychiatric disorders. Science 353:772–77
    [Google Scholar]
  40. Eyo UB, Gu N, De S, Dong H, Richardson JR, Wu LJ 2015. Modulation of microglial process convergence toward neuronal dendrites by extracellular calcium. J. Neurosci. 35:2417–22
    [Google Scholar]
  41. Fang Q, Strand A, Law W, Faca VM, Fitzgibbon MP et al. 2009. Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease. Mol. Cell Proteom. 8:451–66
    [Google Scholar]
  42. Feinberg I. 1982. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence?. J. Psychiatr. Res. 17:319–34
    [Google Scholar]
  43. Filipello F, Morini R, Corradini I, Zerbi V, Canzi A et al. 2018. The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity. Immunity 48:979–91.e8
    [Google Scholar]
  44. Fruhbeis C, Frohlich D, Kuo WP, Kramer-Albers EM 2013. Extracellular vesicles as mediators of neuron-glia communication. Front. Cell Neurosci. 7:182
    [Google Scholar]
  45. Fuentes-Medel Y, Logan MA, Ashley J, Ataman B, Budnik V, Freeman MR 2009. Glia and muscle sculpt neuromuscular arbors by engulfing destabilized synaptic boutons and shed presynaptic debris. PLOS Biol 7:e1000184
    [Google Scholar]
  46. Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T et al. 1996. A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Mol. Cell Biol. 16:6887–99
    [Google Scholar]
  47. Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C et al. 2018. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia and bipolar disorder. Science 362:6420eaat8127
    [Google Scholar]
  48. Gardiner EJ, Cairns MJ, Liu B, Beveridge NJ, Carr V et al. 2013. Gene expression analysis reveals schizophrenia-associated dysregulation of immune pathways in peripheral blood mononuclear cells. J. Psychiatr. Res. 47:425–37
    [Google Scholar]
  49. Glantz LA, Lewis DA. 2000. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 57:65–73
    [Google Scholar]
  50. Goda Y, Davis GW. 2003. Mechanisms of synapse assembly and disassembly. Neuron 40:243–64
    [Google Scholar]
  51. Goodman CS, Shatz CJ. 1993. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72:77–98
    [Google Scholar]
  52. Gould SJ, Raposo G. 2013. As we wait: coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles 2:20389
    [Google Scholar]
  53. Graveland GA, Williams RS, DiFiglia M 1985. Evidence for degenerative and regenerative changes in neo-striatal spiny neurons in Huntington's disease. Science 227:770–73
    [Google Scholar]
  54. Grigoryan T, Birchmeier W. 2015. Molecular signaling mechanisms of axon-glia communication in the peripheral nervous system. Bioessays 37:502–13
    [Google Scholar]
  55. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E et al. 2013. TREM2 variants in Alzheimer's disease. N. Engl. J. Med. 368:117–27
    [Google Scholar]
  56. Guido W. 2008. Refinement of the retinogeniculate pathway. J. Physiol. 586:4357–62
    [Google Scholar]
  57. Hammond TR, Dufort C, Disseng-Olesen L, Giera S, Young A et al. 2018a. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50:253–271.e6
    [Google Scholar]
  58. Hammond TR, Robinton D, Stevens B 2018b. Microglia and the brain: complementary partners in development and disease. Annu. Rev. Cell Dev. Biol. 34:523–44
    [Google Scholar]
  59. Holm MM, Kaiser J, Schwab ME 2018. Extracellular vesicles: multimodal envoys in neural maintenance and repair. Trends Neurosci 41:360–72
    [Google Scholar]
  60. Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S et al. 2016. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352:712–16
    [Google Scholar]
  61. Hoshiko M, Arnoux I, Avignone E, Yamamoto N, Audinat E 2012. Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex. J. Neurosci. 32:15106–11
    [Google Scholar]
  62. Huberman AD, Feller MB, Chapman B 2008. Mechanisms underlying development of visual maps and receptive fields. Annu. Rev. Neurosci. 31:479–509
    [Google Scholar]
  63. Hutsler JJ, Zhang H. 2010. Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res 1309:83–94
    [Google Scholar]
  64. Janssen B, Vugts DJ, Funke U, Molenaar GT, Kruijer PS et al. 2016. Imaging of neuroinflammation in Alzheimer's disease, multiple sclerosis and stroke: recent developments in positron emission tomography. Biochim. Biophys. Acta 1862:425–41
    [Google Scholar]
  65. Ji K, Akgul G, Wollmuth LP, Tsirka SE 2013. Microglia actively regulate the number of functional synapses. PLOS ONE 8:e56293
    [Google Scholar]
  66. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C 1987. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262:9412–20
    [Google Scholar]
  67. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV et al. 2013. Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med. 368:107–16
    [Google Scholar]
  68. Kano M, Hashimoto K. 2009. Synapse elimination in the central nervous system. Curr. Opin. Neurobiol. 19:154–61
    [Google Scholar]
  69. Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A 1997. A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature 386:181–86
    [Google Scholar]
  70. Kim HJ, Cho MH, Shim WH, Kim JK, Jeon EY et al. 2017. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol. Psychiatry 22:1576–84
    [Google Scholar]
  71. Kim T, Vidal GS, Djurisic M, William CM, Birnbaum ME et al. 2013. Human LilrB2 is a β-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer's model. Science. 34161521399–404
  72. Kolluri N, Sun Z, Sampson AR, Lewis DA 2005. Lamina-specific reductions in dendritic spine density in the prefrontal cortex of subjects with schizophrenia. Am. J. Psychiatry 162:1200–2
    [Google Scholar]
  73. Koropouli E, Kolodkin AL. 2014. Semaphorins and the dynamic regulation of synapse assembly, refinement, and function. Curr. Opin. Neurobiol. 27:1–7
    [Google Scholar]
  74. Kuo CT, Jan LY, Jan YN 2005. Dendrite-specific remodeling of Drosophila sensory neurons requires matrix metalloproteases, ubiquitin-proteasome, and ecdysone signaling. PNAS 102:15230–35
    [Google Scholar]
  75. Kuo CT, Zhu S, Younger S, Jan LY, Jan YN 2006. Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Neuron 51:283–90
    [Google Scholar]
  76. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R et al. 2013. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat. Genet. 45:1452–58
    [Google Scholar]
  77. Lee YI, Li Y, Mikesh M, Smith I, Nave KA et al. 2016. Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions. PNAS 113:E479–87
    [Google Scholar]
  78. Lee YI, Thompson WJ, Harlow ML 2017. Schwann cells participate in synapse elimination at the developing neuromuscular junction. Curr. Opin. Neurobiol. 47:176–81
    [Google Scholar]
  79. Lehrman EK, Wilton DK, Litvina EY, Welsh CA, Chang ST et al. 2018. CD47 protects synapses from excess microglia-mediated pruning during development. Neuron 100:120–34
    [Google Scholar]
  80. Lewis JD, Theilmann RJ, Fonov V, Bellec P, Lincoln A et al. 2013. Callosal fiber length and interhemispheric connectivity in adults with autism: brain overgrowth and underconnectivity. Hum. Brain Mapp. 34:1685–95
    [Google Scholar]
  81. Li Y, Du XF, Liu CS, Wen ZL, Du JL 2012. Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo. Dev. Cell 23:1189–202
    [Google Scholar]
  82. Lichtman JW, Colman H. 2000. Synapse elimination and indelible memory. Neuron 25:269–78
    [Google Scholar]
  83. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ et al. 2017. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–87
    [Google Scholar]
  84. Lieberman OJ, McGuirt AF, Tang G, Sulzer D 2019. Roles for neuronal and glial autophagy in synaptic pruning during development. Neurobiol. Dis 122:49–63
    [Google Scholar]
  85. Liu X, Bates R, Yin DM, Shen C, Wang F et al. 2011. Specific regulation of NRG1 isoform expression by neuronal activity. J. Neurosci. 31:8491–501
    [Google Scholar]
  86. Logan MA, Hackett R, Doherty J, Sheehan A, Speese SD, Freeman MR 2012. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury. Nat. Neurosci. 15:722–30
    [Google Scholar]
  87. Lopez-Murcia FJ, Terni B, Llobet A 2015. SPARC triggers a cell-autonomous program of synapse elimination. PNAS 112:13366–71
    [Google Scholar]
  88. Lui H, Zhang J, Makinson SR, Cahill MK, Kelley KW et al. 2016. Progranulin deficiency promotes circuit-specific synaptic pruning by microglia via complement activation. Cell 165:921–35
    [Google Scholar]
  89. Ma Y, Ramachandran A, Ford N, Parada I, Prince DA 2013. Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy. Epilepsia 54:1232–39
    [Google Scholar]
  90. Macdonald JM, Doherty J, Hackett R, Freeman MR 2013. The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of Draper and phagocytic function. Cell Death Differ 20:1140–48
    [Google Scholar]
  91. Marei HE, Althani A, Suhonen J, El Zowalaty ME, Albanna MA et al. 2016. Common and rare genetic variants associated with Alzheimer's disease. J. Cell Physiol. 231:1432–37
    [Google Scholar]
  92. Margeta MA, Shen K. 2010. Molecular mechanisms of synaptic specificity. Mol. Cell. Neurosci. 43:261–67
    [Google Scholar]
  93. Mason CA, Christakos S, Catalano SM 1990. Early climbing fiber interactions with Purkinje cells in the postnatal mouse cerebellum. J. Comp. Neurol. 297:77–90
    [Google Scholar]
  94. Matozaki T, Murata Y, Okazawa H, Ohnishi H 2009. Functions and molecular mechanisms of the CD47–SIRPα signalling pathway. Trends Cell Biol 19:72–80
    [Google Scholar]
  95. Michalski JP, Kothary R. 2015. Oligodendrocytes in a nutshell. Front. Cell Neurosci. 9:340
    [Google Scholar]
  96. Milnerwood AJ, Raymond LA. 2010. Early synaptic pathophysiology in neurodegeneration: insights from Huntington's disease. Trends Neurosci 33:513–23
    [Google Scholar]
  97. Musashe DT, Purice MD, Speese SD, Doherty J, Logan MA 2016. Insulin-like signaling promotes glial phagocytic clearance of degenerating axons through regulation of Draper. Cell Rep 16:1838–50
    [Google Scholar]
  98. Nardone S, Sams DS, Reuveni E, Getselter D, Oron O et al. 2014. DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. Transl. Psychiatry 4:e433
    [Google Scholar]
  99. Nelson LH, Lenz KM. 2017. Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats. Behav. Brain Res. 316:279–93
    [Google Scholar]
  100. Neniskyte U, Gross CT. 2017. Errant gardeners: glial-cell-dependent synaptic pruning and neurodevelopmental disorders. Nat. Rev. Neurosci. 18:658–70
    [Google Scholar]
  101. Norris GT, Smirnov I, Filiano AJ, Shadowen HM, Cody KR et al. 2018. Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury. J. Exp. Med. 215:1789–801
    [Google Scholar]
  102. O'Brien RA, Ostberg AJ, Vrbova G 1978. Observations on the elimination of polyneuronal innervation in developing mammalian skeletal muscle. J. Physiol. 282:571–82
    [Google Scholar]
  103. Paloneva J, Autti T, Raininko R, Partanen J, Salonen O et al. 2001. CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. Neurology 56:1552–58
    [Google Scholar]
  104. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M et al. 2011. Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456–58
    [Google Scholar]
  105. Paolicelli RC, Jawaid A, Henstridge CM, Valeri A, Merlini M et al. 2017. TDP-43 depletion in microglia promotes amyloid clearance but also induces synapse loss. Neuron 95:297–308.e6
    [Google Scholar]
  106. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd et al. 2013. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596–609
    [Google Scholar]
  107. Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F et al. 2006. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 66:1638–43
    [Google Scholar]
  108. Penn AA, Riquelme PA, Feller MB, Shatz CJ 1998. Competition in retinogeniculate patterning driven by spontaneous activity. Science 279:2108–12
    [Google Scholar]
  109. Personius KE, Balice-Gordon RJ. 2002. Activity-dependent synaptic plasticity: insights from neuromuscular junctions. Neuroscientist 8:414–22
    [Google Scholar]
  110. Picconi B, Piccoli G, Calabresi P 2012. Synaptic dysfunction in Parkinson's disease. Adv. Exp. Med. Biol. 970:553–72
    [Google Scholar]
  111. Prada I, Gabrielli M, Turola E, Iorio A, D'Arrigo G et al. 2018. Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations. Acta Neuropathol 135:529–50
    [Google Scholar]
  112. Rayaprolu S, Mullen B, Baker M, Lynch T et al. 2013. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease. Mol. Neurodegener. 8:19
    [Google Scholar]
  113. Riccomagno MM, Kolodkin AL. 2015. Sculpting neural circuits by axon and dendrite pruning. Annu. Rev. Cell Dev. Biol. 31:779–805
    [Google Scholar]
  114. Ridge RM, Betz WJ. 1984. The effect of selective, chronic stimulation on motor unit size in developing rat muscle. J. Neurosci. 4:2614–20
    [Google Scholar]
  115. Risher WC, Patel S, Kim IH, Uezu A, Bhagat S et al. 2014. Astrocytes refine cortical connectivity at dendritic spines. eLife 3:e04047
    [Google Scholar]
  116. Roche SL, Sherman DL, Dissanayake K, Soucy G, Desmazieres A et al. 2014. Loss of glial neurofascin155 delays developmental synapse elimination at the neuromuscular junction. J. Neurosci. 34:12904–18
    [Google Scholar]
  117. Roumier A, Bechade C, Poncer JC, Smalla KH, Tomasello E et al. 2004. Impaired synaptic function in the microglial KARAP/DAP12-deficient mouse. J. Neurosci. 24:11421–28
    [Google Scholar]
  118. Salter MW, Stevens B. 2017. Microglia emerge as central players in brain disease. Nat. Med. 23:1018–27
    [Google Scholar]
  119. Sanes JR, Lichtman JW. 1999. Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22:389–442
    [Google Scholar]
  120. Schafer DP, Heller CT, Gunner G, Heller M, Gordon C et al. 2016. Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression. eLife 5:e15224
    [Google Scholar]
  121. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR et al. 2012. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691–705
    [Google Scholar]
  122. Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR et al. 2016. Schizophrenia risk from complex variation of complement component 4. Nature 530:177–83
    [Google Scholar]
  123. Selkoe DJ. 2002. Alzheimer's disease is a synaptic failure. Science 298:789–91
    [Google Scholar]
  124. Sengpiel F, Kind PC. 2002. The role of activity in development of the visual system. Curr. Biol. 12:R818–26
    [Google Scholar]
  125. Shaham S. 2015. Glial development and function in the nervous system of Caenorhabditis elegans. . Cold Spring Harb. Perspect. Biol 7:a020578
    [Google Scholar]
  126. Shatz CJ. 1983. The prenatal development of the cat's retinogeniculate pathway. J. Neurosci. 3:482–99
    [Google Scholar]
  127. Shatz CJ, Stryker MP. 1988. Prenatal tetrodotoxin infusion blocks segregation of retinogeniculate afferents. Science 242:87–89
    [Google Scholar]
  128. Shi Q, Chowdhury S, Ma R, Le KX, Hong S et al. 2017. Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice. Sci. Transl. Med 9:eaaf6295
    [Google Scholar]
  129. Simon DJ, Weimer RM, McLaughlin T, Kallop D, Stanger K et al. 2012. A caspase cascade regulating developmental axon degeneration. J. Neurosci. 32:17540–53
    [Google Scholar]
  130. Simons M, Nave KA. 2015. Oligodendrocytes: myelination and axonal support. Cold Spring Harb. Perspect. Biol. 8:a020479
    [Google Scholar]
  131. Singh SK, Stogsdill JA, Pulimood NS, Dingsdale H, Kim YH et al. 2016. Astrocytes assemble thalamocortical synapses by bridging NRX1α and NL1 via hevin. Cell 164:183–96
    [Google Scholar]
  132. Sipe GO, Lowery RL, Tremblay ME, Kelly EA, Lamantia CE, Majewska AK 2016. Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex. Nat. Commun. 7:a10905
    [Google Scholar]
  133. Smith IW, Mikesh M, Lee Y, Thompson WJ 2013. Terminal Schwann cells participate in the competition underlying neuromuscular synapse elimination. J. Neurosci. 33:17724–36
    [Google Scholar]
  134. Sretavan DW, Kruger K. 1998. Randomized retinal ganglion cell axon routing at the optic chiasm of GAP-43-deficient mice: association with midline recrossing and lack of normal ipsilateral axon turning. J. Neurosci. 18:10502–13
    [Google Scholar]
  135. Stellwagen D, Shatz CJ. 2002. An instructive role for retinal waves in the development of retinogeniculate connectivity. Neuron 33:357–67
    [Google Scholar]
  136. Stephan AH, Barres BA, Stevens B 2012. The complement system: an unexpected role in synaptic pruning during development and disease. Annu. Rev. Neurosci. 35:369–89
    [Google Scholar]
  137. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS et al. 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131:1164–78
    [Google Scholar]
  138. Stogsdill JA, Eroglu C. 2017. The interplay between neurons and glia in synapse development and plasticity. Curr. Opin. Neurobiol. 42:1–8
    [Google Scholar]
  139. Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Futatsubashi M et al. 2013. Microglial activation in young adults with autism spectrum disorder. JAMA Psychiatry 70:49–58
    [Google Scholar]
  140. Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA et al. 2007. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain 130:1759–66
    [Google Scholar]
  141. Tasdemir-Yilmaz OE, Freeman MR. 2014. Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Genes Dev 28:20–33
    [Google Scholar]
  142. Terni B, Lopez-Murcia FJ, Llobet A 2017. Role of neuron-glia interactions in developmental synapse elimination. Brain Res. Bull. 129:74–81
    [Google Scholar]
  143. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R et al. 1991. Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30:572–80
    [Google Scholar]
  144. Thompson W, Kuffler DP, Jansen JK 1979. The effect of prolonged, reversible block of nerve impulses on the elimination of polyneuronal innervation of new-born rat skeletal muscle fibers. Neuroscience 4:271–81
    [Google Scholar]
  145. Torres L, Danver J, Ji K, Miyauchi JT, Chen D et al. 2016. Dynamic microglial modulation of spatial learning and social behavior. Brain Behav. Immun. 55:6–16
    [Google Scholar]
  146. Tran TS, Rubio ME, Clem RL, Johnson D, Case L et al. 2009. Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS. Nature 462:1065–69
    [Google Scholar]
  147. Tremblay ME, Lowery RL, Majewska AK 2010. Microglial interactions with synapses are modulated by visual experience. PLOS Biol 8:e1000527
    [Google Scholar]
  148. Vainchtein ID, Chin G, Cho FS, Kelley KW, Miller JG et al. 2018. Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development. Science 359:1269–73
    [Google Scholar]
  149. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA 2005. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 57:67–81
    [Google Scholar]
  150. Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B et al. 2016. A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature 534:538–43
    [Google Scholar]
  151. Vincent AJ, Lau PW, Roskams AJ 2008. SPARC is expressed by macroglia and microglia in the developing and mature nervous system. Dev. Dyn. 237:1449–62
    [Google Scholar]
  152. Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y et al. 2011. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474:380–84
    [Google Scholar]
  153. Watts RJ, Hoopfer ED, Luo L 2003. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron 38:871–85
    [Google Scholar]
  154. Watts RJ, Schuldiner O, Perrino J, Larsen C, Luo L 2004. Glia engulf degenerating axons during developmental axon pruning. Curr. Biol. 14:678–84
    [Google Scholar]
  155. Weinhard L, di Bartolomei G, Bolasco G, Machado P, Schieber NL et al. 2018. Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction. Nat. Commun. 9:1228
    [Google Scholar]
  156. Williams PA, Tribble JR, Pepper KW, Cross SD, Morgan BP et al. 2016. Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma. Mol. Neurodegener. 11:26
    [Google Scholar]
  157. Wishart TM, Parson SH, Gillingwater TH 2006. Synaptic vulnerability in neurodegenerative disease. J. Neuropathol. Exp. Neurol. 65:733–39
    [Google Scholar]
  158. Xu J, Sun J, Chen J, Wang L, Li A et al. 2012. RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia. BMC Genom 13:Suppl. 8S2
    [Google Scholar]
  159. Xu NJ, Sun S, Gibson JR, Henkemeyer M 2011. A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses. Nat. Neurosci. 14:1421–29
    [Google Scholar]
  160. Yang J, Yang H, Liu Y, Li X, Qin L et al. 2016. Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP. eLife 5:e15043
    [Google Scholar]
  161. Zemmar A, Chen CC, Weinmann O, Kast B, Vajda F et al. 2018. Oligodendrocyte- and neuron-specific Nogo-A restrict dendritic branching and spine density in the adult mouse motor cortex. Cereb. Cortex 28:2109–17
    [Google Scholar]
  162. Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G et al. 2014. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17:400–6
    [Google Scholar]
  163. Zhang Y, Catts VS, Sheedy D, McCrossin T, Kril JJ, Shannon Weickert C 2016. Cortical grey matter volume reduction in people with schizophrenia is associated with neuro-inflammation. Transl. Psychiatry 6:e982
    [Google Scholar]
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