CoChat
Sign Up
Cited by 87Neuroscience and Neuropharmacology ResearchAutophagy in Disease and TherapyGenetics and Neurodevelopmental Disorders

Roles for neuronal and glial autophagy in synaptic pruning during development

Open access
Lieberman, Ori J., McGuirt, Avery F., Tang, Guomei, Sulzer, David·2019·Neurobiology of Disease
DOI 10.1016/j.nbd.2018.04.017PMC PMC6204314
Open this paper in CoChat — free account

Abstract

The dendritic protrusions known as spines represent the primary postsynaptic location for excitatory synapses. Dendritic spines are critical for many synaptic functions, and their formation, modification, and turnover are thought to be important for mechanisms of learning and memory. At many excitatory synapses, dendritic spines form during the early postnatal period, and while many spines are likely being formed and removed throughout life, the net number are often gradually "pruned" during adolescence to reach a stable level in the adult. In neurodevelopmental disorders, spine pruning is disrupted, emphasizing the importance of understanding its governing processes. Autophagy, a process through which cytosolic components and organelles are degraded, has recently been shown to control spine pruning in the mouse cortex, but the mechanisms through which autophagy acts remain obscure. Here, we draw on three widely studied prototypical synaptic pruning events to focus on two governing principles of spine pruning: 1) activity-dependent synaptic competition and 2) non-neuronal contributions. We briefly review what is known about autophagy in the central nervous system and its regulation by metabolic kinases. We propose a model in which autophagy in both neurons and non-neuronal cells contributes to spine pruning, and how other processes that regulate spine pruning could intersect with autophagy. We further outline future research directions to address outstanding questions on the role of autophagy in synaptic pruning.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.nbd.2018.04.017

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Glial autophagy, particularly in microglia and astrocytes, regulates synaptic pruning and Aβ clearance.

    “Glial autophagy, particularly in microglia and astrocytes, regulates synaptic pruning and Aβ clearance; its impairment may shift glia toward proinflammatory phenotypes [142].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [142]

    Sections VII–VIII support a role for microglial autophagy in synaptic pruning, and Section II describes astrocytes engulfing synapses during pruning. The cited passages do not establish that astrocyte autophagy regulates pruning or that glial autophagy clears Aβ. They also do not support the citing sentence’s claim that impaired glial autophagy shifts glia toward proinflammatory phenotypes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Impairment of glial autophagy may shift glia toward proinflammatory phenotypes.

    “Glial autophagy, particularly in microglia and astrocytes, regulates synaptic pruning and Aβ clearance; its impairment may shift glia toward proinflammatory phenotypes [142].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [142]

    Section V says peripheral inflammatory insults can inhibit autophagic function in the brain, but does not say that impaired glial autophagy shifts glia toward proinflammatory phenotypes. Sections VII–VIII discuss microglial autophagy in synaptic pruning without addressing that proposed shift. Searches for proinflammatory phenotypes and inflammatory responses to impaired microglial autophagy found no supporting passage. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 186

  1. Adams L Goldman D 1998 Role for calcium from the sarcoplasmic reticulum in coupling muscle activity to nicotinic acetylcholine receptor gene expression in rat J Neurobiol 35 245 257 10.1002/(SICI)1097-4695(19980605)35:3<245::AID-NEU2>3.0.CO;2-Z 9622008 · DOI
  2. 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 10.1002/cne.901450402 5044254 · DOI · Paper page
  3. Alvarez VA Sabatini BL 2007 Anatomical and physiological plasticity of dendritic spines Annu Rev Neurosci 30 79 97 10.1146/annurev.neuro.30.051606.094222 17280523 · DOI · Paper page
  4. Auerbach BD Osterweil EK Bear MF 2011 Mutations causing syndromic autism define an axis of synaptic pathophysiology Nature 480 63 68 10.1038/nature10658 22113615 PMC3228874 · DOI · Paper page
  5. Backer JM 2008 The regulation and function of Class III PI3Ks: novel roles for Vps34 Biochem J 410 1 17 10.1042/BJ20071427 18215151 · DOI
  6. Balice-Gordon RJ Lichtman JW 1993 In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions J Neurosci 13 834 855 8426240 PMC6576660
  7. Bateup HS Johnson CA Denefrio CL Saulnier JL Kornacker K Sabatini BL 2013 Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis Neuron 78 510 522 10.1016/j.neuron.2013.03.017 23664616 PMC3690324 · DOI
  8. Bateup HS Takasaki KT Saulnier JL Denefrio CL Sabatini BL 2011 Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function J Neurosci 31 8862 8869 10.1523/JNEUROSCI.1617-11.2011 21677170 PMC3133739 · DOI · Paper page
  9. Becker N Wierenga CJ Fonseca R Bonhoeffer T Nägerl UV 2008 LTD induction causes morphological changes of presynaptic boutons and reduces their contacts with spines Neuron 60 590 597 10.1016/j.neuron.2008.09.018 19038217 · DOI
  10. Berthet A Margolis EB Zhang Jue Hsieh I Zhang Jiasheng Hnasko TS Ahmad J Edwards RH Sesaki H Huang EJ Nakamura K 2014 Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons J Neurosci 34 14304 14317 10.1523/JNEUROSCI.0930-14.2014 25339743 PMC4205554 · DOI
  11. Bindokas VP Lee CC Colmers WF Miller RJ 1998 Changes in mitochondrial function resulting from synaptic activity in the rat hippocampal slice J Neurosci 18 4570 4587 9614233 PMC6792701
  12. Bishop DL Misgeld T Walsh MK Gan WB Lichtman JW 2004 Axon branch removal at developing synapses by axosome shedding Neuron 44 651 661 10.1016/j.neuron.2004.10.026 15541313 · DOI
  13. Bjartmar L Huberman AD Ullian EM Rentería RC Liu X Xu W Prezioso J Susman MW Stellwagen D Stokes CC Cho R Worley P Malenka RC Ball S Peachey NS Copenhagen D Chapman B Nakamoto M Barres BA Perin MS 2006 Neuronal pentraxins mediate synaptic refinement in the developing visual system J Neurosci 26 6269 6281 10.1523/JNEUROSCI.4212-05.2006 16763034 PMC2579897 · DOI · Paper page
  14. Bockaert J Marin P 2015 mTOR in Brain Physiology and Pathologies Physiol Rev 95 1157 1187 10.1152/physrev.00038.2014 26269525 · DOI
  15. Bosman LWJ Takechi H Hartmann J Eilers J Konnerth A 2008 Homosynaptic long-term synaptic potentiation of the “winner” climbing fiber synapse in developing Purkinje cells J Neurosci 28 798 807 10.1523/JNEUROSCI.4074-07.2008 18216188 PMC6671003 · DOI
  16. 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 424 430 434 10.1038/nature01844 12879071 · DOI
  17. Buffelli M Busetto G Cangiano L Cangiano A 2002 Perinatal switch from synchronous to asynchronous activity of motoneurons: link with synapse elimination Proc Natl Acad Sci USA 99 13200 13205 10.1073/pnas.202471199 12242340 PMC130610 · DOI
  18. 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 10.1371/journal.pbio.0050061 17341130 PMC1808114 · DOI · Paper page
  19. Cai Q Zakaria HM Simone A Sheng ZH 2012 Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons Curr Biol 22 545 552 10.1016/j.cub.2012.02.005 22342752 PMC3313683 · DOI
  20. Cameron HA Kaliszewski CK Greer CA 1991 Organization of mitochondria in olfactory bulb granule cell dendritic spines Synapse 8 107 118 10.1002/syn.890080205 1715612 · DOI
  21. Cariboni A Davidson K Rakic S Maggi R Parnavelas JG Ruhrberg C 2011 Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism Hum Mol Genet 20 336 344 10.1093/hmg/ddq468 21059704 · DOI
  22. Carrillo J Nishiyama N Nishiyama H 2013 Dendritic translocation establishes the winner in cerebellar climbing fiber synapse elimination J Neurosci 33 7641 7653 10.1523/JNEUROSCI.4561-12.2013 23637158 PMC3697481 · DOI
  23. Chada SR Hollenbeck PJ 2004 Nerve growth factor signaling regulates motility and docking of axonal mitochondria Curr Biol 14 1272 1276 10.1016/j.cub.2004.07.027 15268858 · DOI
  24. Chedotal A Sotelo C 1993 The “creeper stage” in cerebellar climbing fiber synaptogenesis precedes the “pericellular nest”--ultrastructural evidence with parvalbumin immunocytochemistry Brain Res Dev Brain Res 76 207 220 8149587
  25. Chen J Billings SE Nishimune H 2011 Calcium channels link the muscle-derived synapse organizer laminin β2 to Bassoon and CAST/Erc2 to organize presynaptic active zones J Neurosci 31 512 525 10.1523/JNEUROSCI.3771-10.2011 21228161 PMC3723116 · DOI
  26. Chow I Poo MM 1985 Release of acetylcholine from embryonic neurons upon contact with muscle cell J Neurosci 5 1076 1082 3884749 PMC6564999
  27. Chu Y Jin X Parada I Pesic A Stevens B Barres B Prince DA 2010 Enhanced synaptic connectivity and epilepsy in C1q knockout mice Proc Natl Acad Sci USA 107 7975 7980 10.1073/pnas.0913449107 20375278 PMC2867906 · DOI · Paper page
  28. Cingolani LA Goda Y 2008 Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy Nat Rev Neurosci 9 344 356 10.1038/nrn2373 18425089 · DOI · Paper page
  29. Clausen BE Burkhardt C Reith W Renkawitz R Förster I 1999 Conditional gene targeting in macrophages and granulocytes using LysMcre mice Transgenic Res 8 265 277 10621974
  30. Colman H Nabekura J Lichtman JW 1997 Alterations in synaptic strength preceding axon withdrawal Science (80-) 275 356 361 8994026
  31. Coly PM Gandolfo P Castel H Morin F 2017 The autophagy machinery: A new player in chemotactic cell migration Front Neurosci 11 78 10.3389/fnins.2017.00078 28261054 PMC5311050 · DOI
  32. Courchet J Lewis TL Lee S Courchet V Liou DY Aizawa S Polleux F 2013 Terminal axon branching is regulated by the LKB1-NUAK1 kinase pathway via presynaptic mitochondrial capture Cell 153 1510 1525 10.1016/j.cell.2013.05.021 23791179 PMC3729210 · DOI
  33. Crepel F Delhaye-Bouchaud N Dupont JL 1981 Fate of the multiple innervation of cerebellar Purkinje cells by climbing fibers in immature control, x-irradiated and hypothyroid rats Brain Res 227 59 71 7470934
  34. Cubells JF Rayport S Rajendran G Sulzer D 1994 Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress J Neurosci 14 2260 2271 8158268 PMC6577123
  35. Dadalko OI Siuta M Poe A Erreger K Matthies HJG Niswender K Galli A 2015 mTORC2/rictor signaling disrupts dopamine-dependent behaviors via defects in striatal dopamine neurotransmission J Neurosci 35 8843 8854 10.1523/JNEUROSCI.0887-15.2015 26063917 PMC4461689 · DOI
  36. Dai Z Peng HB 1993 Elevation in presynaptic Ca2+ level accompanying initial nerve-muscle contact in tissue culture Neuron 10 827 837 8098609
  37. Darabid H Arbour D Robitaille R 2013 Glial cells decipher synaptic competition at the mammalian neuromuscular junction J Neurosci 33 1297 1313 10.1523/JNEUROSCI.2935-12.2013 23345206 PMC6618718 · DOI
  38. Datwani A McConnell MJ Kanold PO Micheva KD Busse B Shamloo M Smith SJ Shatz CJ 2009 Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity Neuron 64 463 470 10.1016/j.neuron.2009.10.015 19945389 PMC2787480 · DOI · Paper page
  39. Depino AM 2017 Perinatal inflammation and adult psychopathology: From preclinical models to humans Semin Cell Dev Biol 10.1016/j.semcdb.2017.09.010 28890420 · DOI
  40. Di Nardo A Wertz MH Kwiatkowski E Tsai PT Leech JD Greene-Colozzi E Goto J Dilsiz P Talos DM Clish CB Kwiatkowski DJ Sahin M 2014 Neuronal Tsc1/2 complex controls autophagy through AMPK-dependent regulation of ULK1 Hum Mol Genet 23 3865 3874 10.1093/hmg/ddu101 24599401 PMC4065158 · DOI
  41. Dölen G Bear MF 2009 Fragile x syndrome and autism: from disease model to therapeutic targets J Neurodev Disord 1 133 140 10.1007/s11689-009-9015-x 21547712 PMC3164025 · DOI
  42. Dunlop EA Tee AR 2014 mTOR and autophagy: a dynamic relationship governed by nutrients and energy Semin Cell Dev Biol 36 121 129 10.1016/j.semcdb.2014.08.006 25158238 · DOI
  43. Ebrahimi-Fakhari D Saffari A Wahlster L Di Nardo A Turner D Lewis TL Conrad C Rothberg JM Lipton JO Kölker S Hoffmann GF Han MJ Polleux F Sahin M 2016 Impaired mitochondrial dynamics and mitophagy in neuronal models of tuberous sclerosis complex Cell Rep 17 1053 1070 10.1016/j.celrep.2016.09.054 27760312 PMC5078873 · DOI · Paper page
  44. European Chromosome 16 Tuberous Sclerosis Consortium 1993 Identification and characterization of the tuberous sclerosis gene on chromosome 16 Cell 75 1305 1315 10.1016/0092-8674(93)90618-Z 8269512 · DOI · Paper page
  45. Evers J Laser M Sun YA Xie ZP Poo MM 1989 Studies of nerve-muscle interactions in Xenopus cell culture: analysis of early synaptic currents J Neurosci 9 1523 1539 2723739 PMC6569819
  46. Favero M Busetto G Cangiano A 2012 Spike timing plays a key role in synapse elimination at the neuromuscular junction Proc Natl Acad Sci USA 109 E1667 75 10.1073/pnas.1201147109 22619332 PMC3382556 · DOI
  47. Fox MA Sanes JR Borza DB Eswarakumar VP Fässler R Hudson BG John SWM Ninomiya Y Pedchenko V Pfaff SL Rheault MN Sado Y Segal Y Werle MJ Umemori H 2007 Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals Cell 129 179 193 10.1016/j.cell.2007.02.035 17418794 · DOI
  48. François A Terro F Quellard N Fernandez B Chassaing D Janet T Rioux Bilan A Paccalin M Page G 2014 Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice Mol Brain 7 56 10.1186/s13041-014-0056-z 25169902 PMC4237961 · DOI
  49. Frank E Fischbach GD 1979 Early events in neuromuscular junction formation in vitro: induction of acetylcholine receptor clusters in the postsynaptic membrane and morphology of newly formed synapses J Cell Biol 83 143 158 511937 PMC2110446
  50. Fu MM Nirschl JJ Holzbaur ELF 2014 LC3 binding to the scaffolding protein JIP1 regulates processive dynein-driven transport of autophagosomes Dev Cell 29 577 590 10.1016/j.devcel.2014.04.015 24914561 PMC4109720 · DOI
  51. Ganley IG Lam DH Wang J Ding X Chen S Jiang X 2009 ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy J Biol Chem 284 12297 12305 10.1074/jbc.M900573200 19258318 PMC2673298 · DOI
  52. Gasque P 2004 Complement: a unique innate immune sensor for danger signals Mol Immunol 41 1089 1098 10.1016/j.molimm.2004.06.011 15476920 · DOI · Paper page
  53. Gasque P Singhrao SK Neal JW Wang P Sayah S Fontaine M Morgan BP 1998 The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis J Immunol 160 3543 3554 9531317
  54. Goorden SMI van Woerden GM van der Weerd L Cheadle JP Elgersma Y 2007 Cognitive deficits in Tsc1+/− mice in the absence of cerebral lesions and seizures Ann Neurol 62 648 655 10.1002/ana.21317 18067135 · DOI
  55. Hajishengallis G Wang M Liang S 2009 Induction of distinct TLR2-mediated proinflammatory and proadhesive signaling pathways in response to Porphyromonas gingivalis fimbriae J Immunol 182 6690 6696 10.4049/jimmunol.0900524 19454663 PMC2685460 · DOI
  56. Hara T Nakamura K Matsui M Yamamoto A Nakahara Y Suzuki-Migishima R Yokoyama M Mishima K Saito I Okano H Mizushima N 2006 Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice Nature 441 885 889 10.1038/nature04724 16625204 · DOI · Paper page
  57. Hashimoto Kouichi Ichikawa R Kitamura K Watanabe M Kano M 2009 Translocation of a “winner” climbing fiber to the Purkinje cell dendrite and subsequent elimination of “losers” from the soma in developing cerebellum Neuron 63 106 118 10.1016/j.neuron.2009.06.008 19607796 · DOI
  58. Hashimoto K Ichikawa R Takechi H Inoue Y Aiba A Sakimura K Mishina M Hashikawa T Konnerth A Watanabe M Kano M 2001 Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development J Neurosci 21 9701 9712 11739579 PMC6763021
  59. Hashimoto K Kano M 2003 Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum Neuron 38 785 796 10.1016/S0896-6273(03)00298-8 12797962 · DOI
  60. Hashimoto K Kano M 2013 Synapse elimination in the developing cerebellum Cell Mol Life Sci 70 4667 4680 10.1007/s00018-013-1405-2 23811844 PMC3830199 · DOI
  61. Hashimoto K Tsujita M Miyazaki T Kitamura K Yamazaki M Shin HS Watanabe M Sakimura K Kano M 2011 Postsynaptic P/Q-type Ca2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum Proc Natl Acad Sci USA 108 9987 9992 10.1073/pnas.1101488108 21628556 PMC3116426 · DOI
  62. Hashimoto K Yoshida T Sakimura K Mishina M Watanabe M Kano M 2009 Influence of parallel fiber-Purkinje cell synapse formation on postnatal development of climbing fiber-Purkinje cell synapses in the cerebellum Neuroscience 162 601 611 10.1016/j.neuroscience.2008.12.037 19166909 · DOI
  63. Henderson CE Phillips HS Pollock RA Davies AM Lemeulle C Armanini M Simmons L Moffet B Vandlen RA Simmons L Koliatsos VE Rosenthal A 1994 GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle Science (80-) 266 1062 1064 7973664
  64. Hernandez D Torres CA Setlik W Cebrián C Mosharov EV Tang G Cheng HC Kholodilov N Yarygina O Burke RE Gershon M Sulzer D 2012 Regulation of presynaptic neurotransmission by macroautophagy Neuron 74 277 284 10.1016/j.neuron.2012.02.020 22542182 PMC3578406 · DOI
  65. Hevner RF Wong-Riley MT 1993 Mitochondrial and nuclear gene expression for cytochrome oxidase subunits are disproportionately regulated by functional activity in neurons J Neurosci 13 1805 1819 8386752 PMC6576570
  66. Hollenbeck PJ 1993 Products of endocytosis and autophagy are retrieved from axons by regulated retrograde organelle transport J Cell Biol 121 305 315 7682217 PMC2200099
  67. Hooks BM Chen C 2006 Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse Neuron 52 281 291 10.1016/j.neuron.2006.07.007 17046691 · DOI · Paper page
  68. Høyer-Hansen M Bastholm L Szyniarowski P Campanella M Szabadkai G Farkas T Bianchi K Fehrenbacher N Elling F Rizzuto R Mathiasen IS Jäättelä M 2007 Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2 Mol Cell 25 193 205 10.1016/j.molcel.2006.12.009 17244528 · DOI · Paper page
  69. Huang CF Tong J Schmidt J 1992 Protein kinase C couples membrane excitation to acetylcholine receptor gene inactivation in chick skeletal muscle Neuron 9 671 678 1389182
  70. Huberman AD 2007 Mechanisms of eye-specific visual circuit development Curr Opin Neurobiol 17 73 80 10.1016/j.conb.2007.01.005 17254766 · DOI
  71. Hutsler JJ Zhang H 2010 Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders Brain Res 1309 83 94 10.1016/j.brainres.2009.09.120 19896929 · DOI · Paper page
  72. Huttenlocher PR 1990 Morphometric study of human cerebral cortex development Neuropsychologia 28 517 527 10.1016/0028-3932(90)90031-I 2203993 · DOI · Paper page
  73. Huttenlocher PR Dabholkar AS 1997 Regional differences in synaptogenesis in human cerebral cortex J Comp Neurol 387 167 178 10.1002/(SICI)1096-9861(19971020)387:2<167::AID-CNE1>3.0.CO;2-Z 9336221 · DOI
  74. Ichikawa R Miyazaki T Kano M Hashikawa T Tatsumi H Sakimura K Mishina M Inoue Y Watanabe M 2002 Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar Purkinje cells lacking glutamate receptor delta 2 J Neurosci 22 8487 8503 12351723 PMC6757771
  75. Jahromi BS Robitaille R Charlton MP 1992 Transmitter release increases intracellular calcium in perisynaptic Schwann cells in situ Neuron 8 1069 1077 1351731
  76. Je HS Yang F Ji Y Nagappan G Hempstead BL Lu B 2012 Role of pro-brain-derived neurotrophic factor (proBDNF) to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses Proc Natl Acad Sci USA 109 15924 15929 10.1073/pnas.1207767109 23019376 PMC3465384 · DOI · Paper page
  77. Je HS Yang F Ji Y Potluri S Fu XQ Luo ZG Nagappan G Chan JP Hempstead B Son YJ Lu B 2013 ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions J Neurosci 33 9957 9962 10.1523/JNEUROSCI.0163-13.2013 23761891 PMC3682390 · DOI · Paper page
  78. Jiang H Cheng D Liu W Peng J Feng J 2010 Protein kinase C inhibits autophagy and phosphorylates LC3 Biochem Biophys Res Commun 395 471 476 10.1016/j.bbrc.2010.04.030 20398630 PMC2873090 · DOI
  79. Joselin AP Hewitt SJ Callaghan SM Kim RH Chung YH Mak TW Shen J Slack RS Park DS 2012 ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons Hum Mol Genet 21 4888 4903 10.1093/hmg/dds325 22872702 · DOI
  80. Jung CH Jun CB Ro SH Kim YM Otto NM Cao J Kundu M Kim DH 2009 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery Mol Biol Cell 20 1992 2003 10.1091/mbc.E08-12-1249 19225151 PMC2663920 · DOI · Paper page
  81. Jung CH Ro SH Cao J Otto NM Kim DH 2010 mTOR regulation of autophagy FEBS Lett 584 1287 1295 10.1016/j.febslet.2010.01.017 20083114 PMC2846630 · DOI · Paper page
  82. Kakegawa W Mitakidis N Miura E Abe M Matsuda K Takeo YH Kohda K Motohashi J Takahashi A Nagao S Muramatsu S Watanabe M Sakimura K Aricescu AR Yuzaki M 2015 Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum Neuron 85 316 329 10.1016/j.neuron.2014.12.020 25611509 · DOI
  83. Kandt RS Haines JL Smith M Northrup H Gardner RJ Short MP Dumars K Roach ES Steingold S Wall S 1992 Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease Nat Genet 2 37 41 10.1038/ng0992-37 1303246 · DOI
  84. Kang JS Tian JH Pan PY Zald P Li C Deng C Sheng ZH 2008 Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation Cell 132 137 148 10.1016/j.cell.2007.11.024 18191227 PMC2259239 · DOI · Paper page
  85. Kano M Hashimoto K 2009 Synapse elimination in the central nervous system Curr Opin Neurobiol 19 154 161 10.1016/j.conb.2009.05.002 19481442 · DOI
  86. Kano M Hashimoto K Chen C Abeliovich A Aiba A Kurihara H Watanabe M Inoue Y Tonegawa S 1995 Impaired synapse elimination during cerebellar development in PKC gamma mutant mice Cell 83 1223 1231 8548808
  87. Kano M Hashimoto K Kurihara H Watanabe M Inoue Y Aiba A Tonegawa S 1997 Persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking mGluR1 Neuron 18 71 79 9010206
  88. Kano M Hashimoto K Watanabe M Kurihara H Offermanns S Jiang H Wu Y Jun K Shin HS Inoue Y Simon MI Wu D 1998 Phospholipase cbeta4 is specifically involved in climbing fiber synapse elimination in the developing cerebellum Proc Natl Acad Sci USA 95 15724 15729 9861037 PMC28111
  89. Kidokoro Y Yeh E 1982 Initial synaptic transmission at the growth cone in Xenopus nerve-muscle cultures Proc Natl Acad Sci USA 79 6727 6731 6292914 PMC347202
  90. Kim HJ Cho MH Shim WH Kim JK Jeon EY Kim DH Yoon SY 2017 Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects Mol Psychiatry 22 1576 1584 10.1038/mp.2016.103 27400854 PMC5658669 · DOI · Paper page
  91. Kim J Kundu M Viollet B Guan KL 2011 AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 Nat Cell Biol 13 132 141 10.1038/ncb2152 21258367 PMC3987946 · DOI · Paper page
  92. Kimura T Murakami F 2014 Evidence that dendritic mitochondria negatively regulate dendritic branching in pyramidal neurons in the neocortex J Neurosci 34 6938 6951 10.1523/JNEUROSCI.5095-13.2014 24828647 PMC6608104 · DOI
  93. Ko PK Anderson MJ Cohen MW 1977 Denervated skeletal muscle fibers develop discrete patches of high acetylcholine receptor density Science (80-) 196 540 542 850796
  94. Koch C Zador A 1993 The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization J Neurosci 13 413 422 8426220 PMC6576662
  95. Komatsu M Waguri S Chiba T Murata S Iwata J Tanida I Ueno T Koike M Uchiyama Y Kominami E Tanaka K 2006 Loss of autophagy in the central nervous system causes neurodegeneration in mice Nature 441 880 884 10.1038/nature04723 16625205 · DOI · Paper page
  96. Kopp DM Perkel DJ Balice-Gordon RJ 2000 Disparity in neurotransmitter release probability among competing inputs during neuromuscular synapse elimination J Neurosci 20 8771 8779 11102485 PMC6773052
  97. LaMantia AS Rakic P 1990 Axon overproduction and elimination in the corpus callosum of the developing rhesus monkey J Neurosci 10 2156 2175 2376772 PMC6570389
  98. Lanuza MA Garcia N Santafé M González CM Alonso I Nelson PG Tomàs J 2002 Pre- and postsynaptic maturation of the neuromuscular junction during neonatal synapse elimination depends on protein kinase C J Neurosci Res 67 607 617 10.1002/jnr.10122 11891773 · DOI
  99. Larsen KE Fon EA Hastings TG Edwards RH Sulzer D 2002 Methamphetamine-induced degeneration of dopaminergic neurons involves autophagy and upregulation of dopamine synthesis J Neurosci 22 8951 8960 12388602 PMC6757693
  100. Larsen KE Sulzer D 2002 Autophagy in neurons: a review Histol Histopathol 17 897 908 10.14670/HH-17.897 12168801 · DOI
  101. Lee CW Peng HB 2008 The function of mitochondria in presynaptic development at the neuromuscular junction Mol Biol Cell 19 150 158 10.1091/mbc.E07-05-0515 17942598 PMC2174173 · DOI
  102. Lee H Brott BK Kirkby LA Adelson JD Cheng S Feller MB Datwani A Shatz CJ 2014 Synapse elimination and learning rules co-regulated by MHC class I H2-Db Nature 509 195 200 10.1038/nature13154 24695230 PMC4016165 · DOI · Paper page
  103. Levy M Faas GC Saggau P Craigen WJ Sweatt JD 2003 Mitochondrial regulation of synaptic plasticity in the hippocampus J Biol Chem 278 17727 17734 10.1074/jbc.M212878200 12604600 · DOI
  104. Lewis TL Turi GF Kwon SK Losonczy A Polleux F 2016 Progressive Decrease of Mitochondrial Motility during Maturation of Cortical Axons In Vitro and In Vivo Curr Biol 26 2602 2608 10.1016/j.cub.2016.07.064 27641765 PMC5235338 · DOI
  105. Li Z Okamoto KI Hayashi Y Sheng M 2004 The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses Cell 119 873 887 10.1016/j.cell.2004.11.003 15607982 · DOI · Paper page
  106. Lin W Dominguez B Yang J Aryal P Brandon EP Gage FH Lee KF 2005 Neurotransmitter acetylcholine negatively regulates neuromuscular synapse formation by a Cdk5-dependent mechanism Neuron 46 569 579 10.1016/j.neuron.2005.04.002 15944126 · DOI
  107. Lipinski MM Hoffman G Ng A Zhou W Py BF Hsu E Liu X Eisenberg J Liu J Blenis J Xavier RJ Yuan J 2010 A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions Dev Cell 18 1041 1052 10.1016/j.devcel.2010.05.005 20627085 PMC2935848 · DOI
  108. Low LK Liu XB Faulkner RL Coble J Cheng HJ 2008 Plexin signaling selectively regulates the stereotyped pruning of corticospinal axons from visual cortex Proc Natl Acad Sci USA 105 8136 8141 10.1073/pnas.0803849105 18523013 PMC2430372 · DOI
  109. Maday S Holzbaur ELF 2014 Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway Dev Cell 30 71 85 10.1016/j.devcel.2014.06.001 25026034 PMC4109719 · DOI · Paper page
  110. Maday S Holzbaur ELF 2016 Compartment-Specific Regulation of Autophagy in Primary Neurons J Neurosci 36 5933 5945 10.1523/JNEUROSCI.4401-15.2016 27251616 PMC4887563 · DOI · Paper page
  111. Maday S Twelvetrees AE Moughamian AJ Holzbaur ELF 2014 Axonal transport: cargo-specific mechanisms of motility and regulation Neuron 84 292 309 10.1016/j.neuron.2014.10.019 25374356 PMC4269290 · DOI · Paper page
  112. Malkova NV Yu CZ Hsiao EY Moore MJ Patterson PH 2012 Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism Brain Behav Immun 26 607 616 10.1016/j.bbi.2012.01.011 22310922 PMC3322300 · DOI · Paper page
  113. Marques MJ Conchello JA Lichtman JW 2000 From plaque to pretzel: fold formation and acetylcholine receptor loss at the developing neuromuscular junction J Neurosci 20 3663 3675 10804208 PMC6772702
  114. Meikle L Pollizzi K Egnor A Kramvis I Lane H Sahin M Kwiatkowski DJ 2008 Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function J Neurosci 28 5422 5432 10.1523/JNEUROSCI.0955-08.2008 18495876 PMC2633923 · DOI
  115. Mikuni T Uesaka N Okuno H Hirai H Deisseroth K Bito H Kano M 2013 Arc/Arg3.1 is a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum Neuron 78 1024 1035 10.1016/j.neuron.2013.04.036 23791196 PMC3773328 · DOI
  116. Miller BJ Goldsmith DR 2017 Towards an immunophenotype of schizophrenia: progress, potential mechanisms, and future directions Neuropsychopharmacology 42 299 317 10.1038/npp.2016.211 27654215 PMC5143505 · DOI
  117. Misgeld T Kummer TT Lichtman JW Sanes JR 2005 Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter Proc Natl Acad Sci USA 102 11088 11093 10.1073/pnas.0504806102 16043708 PMC1182450 · DOI
  118. Mizushima N Yamamoto A Matsui M Yoshimori T Ohsumi Y 2004 In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker Mol Biol Cell 15 1101 1111 10.1091/mbc.E03-09-0704 14699058 PMC363084 · DOI
  119. Novikoff AB Beaufay H De Duve C 1956 Electron microscopy of lysosomerich fractions from rat liver J Biophys Biochem Cytol 2 179 184 13357540 PMC2229688
  120. Offermanns S Hashimoto K Watanabe M Sun W Kurihara H Thompson RF Inoue Y Kano M Simon MI 1997 Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq Proc Natl Acad Sci USA 94 14089 14094 9391157 PMC28437
  121. Ohsumi Y 2014 Historical landmarks of autophagy research Cell Res 24 9 23 10.1038/cr.2013.169 24366340 PMC3879711 · DOI
  122. Ohtsuki G Hirano T 2008 Bidirectional plasticity at developing climbing fiber-Purkinje neuron synapses Eur J Neurosci 28 2393 2400 10.1111/j.1460-9568.2008.06539.x 19032589 · DOI
  123. Osokine I Erlebacher A 2017 Inflammation and autism: from maternal gut to fetal brain Trends Mol Med 23 1070 1071 10.1016/j.molmed.2017.10.008 29122491 PMC11779533 · DOI
  124. Penn AA Riquelme PA Feller MB Shatz CJ 1998 Competition in retinogeniculate patterning driven by spontaneous activity Science (80-) 279 2108 2112 9516112
  125. Peters A Kaiserman-Abramof IR 1970 The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines Am J Anat 127 321 355 10.1002/aja.1001270402 4985058 · DOI
  126. Phillips M Pozzo-Miller L 2015 Dendritic spine dysgenesis in autism related disorders Neurosci Lett 601 30 40 10.1016/j.neulet.2015.01.011 25578949 PMC4496332 · DOI
  127. Piochon C Kano M Hansel C 2016 LTD-like molecular pathways in developmental synaptic pruning Nat Neurosci 19 1299 1310 10.1038/nn.4389 27669991 PMC5070480 · DOI
  128. Plessinger MA 1998 Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy Obstet Gynecol Clin North Am 25 119 138 9547763
  129. Purves D Lichtman JW 1980 Elimination of synapses in the developing nervous system Science (80-) 210 153 157 7414326
  130. Robitaille R 1998 Modulation of synaptic efficacy and synaptic depression by glial cells at the frog neuromuscular junction Neuron 21 847 855 9808470
  131. Rochon D Rousse I Robitaille R 2001 Synapse-glia interactions at the mammalian neuromuscular junction J Neurosci 21 3819 3829 11356870 PMC6762689
  132. Rowland AM Richmond JE Olsen JG Hall DH Bamber BA 2006 Presynaptic terminals independently regulate synaptic clustering and autophagy of GABAA receptors in Caenorhabditis elegans J Neurosci 26 1711 1720 10.1523/JNEUROSCI.2279-05.2006 16467519 PMC6793639 · DOI · Paper page
  133. Russell RC Tian Y Yuan H Park HW Chang YY Kim J Kim H Neufeld TP Dillin A Guan KL 2013 ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase Nat Cell Biol 15 741 750 10.1038/ncb2757 23685627 PMC3885611 · DOI
  134. Sabatini DD Adesnik M 2013 Christian de Duve: Explorer of the cell who discovered new organelles by using a centrifuge Proc Natl Acad Sci USA 110 13234 13235 10.1073/pnas.1312084110 23924611 PMC3746853 · DOI
  135. Saitsu H Nishimura T Muramatsu K Kodera H Kumada S Sugai K Kasai-Yoshida E Sawaura N Nishida H Hoshino A Ryujin F Yoshioka S Nishiyama K Kondo Y Tsurusaki Y Nakashima M Miyake N Arakawa H Kato M Mizushima N Matsumoto N 2013 De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adulthood Nat Genet 45 445 9 449e1 10.1038/ng.2562 23435086 · DOI · Paper page
  136. Sanjuan MA Dillon CP Tait SWG Moshiach S Dorsey F Connell S Komatsu M Tanaka K Cleveland JL Withoff S Green DR 2007 Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis Nature 450 1253 1257 10.1038/nature06421 18097414 · DOI · Paper page
  137. Sekar A Bialas AR de Rivera H Davis A Hammond TR Kamitaki N Tooley K Presumey J Baum M Van Doren V Genovese G Rose SA Handsaker RE Daly MJ Carroll MC Stevens B McCarroll SA Schizophrenia Working Group of the Psychiatric Genomics Consortium 2016 Schizophrenia risk from complex variation of complement component 4 Nature 530 177 183 10.1038/nature16549 26814963 PMC4752392 · DOI · Paper page
  138. Sharifi MN Mowers EE Drake LE Collier C Chen H Zamora M Mui S Macleod KF 2016 Autophagy Promotes Focal Adhesion Disassembly and Cell Motility of Metastatic Tumor Cells through the Direct Interaction of Paxillin with LC3 Cell Rep 15 1660 1672 10.1016/j.celrep.2016.04.065 27184837 PMC4880529 · DOI
  139. Shatz CJ Stryker MP 1988 Prenatal tetrodotoxin infusion blocks segregation of retinogeniculate afferents Science (80-) 242 87 89 3175636
  140. Shehata M Matsumura H Okubo-Suzuki R Ohkawa N Inokuchi K 2012 Neuronal stimulation induces autophagy in hippocampal neurons that is involved in AMPA receptor degradation after chemical long-term depression J Neurosci 32 10413 10422 10.1523/JNEUROSCI.4533-11.2012 22836274 PMC6703735 · DOI · Paper page
  141. Smit-Rigter L Rajendran R Silva CAP Spierenburg L Groeneweg F Ruimschotel EM van Versendaal D van der Togt C Eysel UT Heimel JA Lohmann C Levelt CN 2016 Mitochondrial dynamics in visual cortex are limited in vivo and not affected by axonal structural plasticity Curr Biol 26 2609 2616 10.1016/j.cub.2016.07.033 27641766 · DOI
  142. Smith IW Mikesh M Lee Yil Thompson WJ 2013 Terminal Schwann cells participate in the competition underlying neuromuscular synapse elimination J Neurosci 33 17724 17736 10.1523/JNEUROSCI.3339-13.2013 24198364 PMC3818548 · DOI
  143. Snider WD Lichtman JW 1996 Are neurotrophins synaptotrophins? Mol Cell Neurosci 7 433 442 10.1006/mcne.1996.0031 8875427 · DOI
  144. Song JW Misgeld T Kang H Knecht S Lu J Cao Y Cotman SL Bishop DL Lichtman JW 2008 Lysosomal activity associated with developmental axon pruning J Neurosci 28 8993 9001 10.1523/JNEUROSCI.0720-08.2008 18768693 PMC2693713 · DOI
  145. Stanton MJ Dutta S Zhang H Polavaram NS Leontovich AA Hönscheid P Sinicrope FA Tindall DJ Muders MH Datta K 2013 Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for treatment resistance Cancer Res 73 160 171 10.1158/0008-5472.CAN-11-3635 23149913 PMC3805049 · DOI
  146. Stellwagen D Shatz CJ 2002 An instructive role for retinal waves in the development of retinogeniculate connectivity Neuron 33 357 367 11832224
  147. Stephan AH Barres BA Stevens B 2012 The complement system: an unexpected role in synaptic pruning during development and disease Annu Rev Neurosci 35 369 389 10.1146/annurev-neuro-061010-113810 22715882 · DOI · Paper page
  148. Stevens B Allen NJ Vazquez LE Howell GR Christopherson KS Nouri N Micheva KD Mehalow AK Huberman AD Stafford B Sher A Litke AM Lambris JD Smith SJ John SWM Barres BA 2007 The classical complement cascade mediates CNS synapse elimination Cell 131 1164 1178 10.1016/j.cell.2007.10.036 18083105 · DOI · Paper page
  149. Sugihara I Wu H Shinoda Y 1999 Morphology of single olivocerebellar axons labeled with biotinylated dextran amine in the rat J Comp Neurol 414 131 148 10.1002/(SICI)1096-9861(19991115)414:2<131::AID-CNE1>3.0.CO;2-F 10516588 · DOI
  150. Sulzer D Mosharov E Talloczy Z Zucca FA Simon JD Zecca L 2008 Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease J Neurochem 106 24 36 10.1111/j.1471-4159.2008.05385.x 18384642 PMC6609458 · DOI
  151. Tang G Gudsnuk K Kuo SH Cotrina ML Rosoklija G Sosunov A Sonders MS Kanter E Castagna C Yamamoto A Yue Z Arancio O Peterson BS Champagne F Dwork AJ Goldman J Sulzer D 2014 Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits Neuron 83 1131 1143 10.1016/j.neuron.2014.07.040 25155956 PMC4159743 · DOI · Paper page
  152. Tang Y Zucker RS 1997 Mitochondrial involvement in post-tetanic potentiation of synaptic transmission Neuron 18 483 491 9115741
  153. Tee AR Manning BD Roux PP Cantley LC Blenis J 2003 Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb Curr Biol 13 1259 1268 10.1016/S0960-9822(03)00506-2 12906785 · DOI
  154. Thompson W 1983 Synapse elimination in neonatal rat muscle is sensitive to pattern of muscle use Nature 302 614 616 6835395
  155. 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 4 271 281 10.1016/0306-4522(79)90088-5 424074 · DOI
  156. Thoreen CC Kang SA Chang JW Liu Q Zhang J Gao Y Reichling LJ Sim T Sabatini DM Gray NS 2009 An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1 J Biol Chem 284 8023 8032 10.1074/jbc.M900301200 19150980 PMC2658096 · DOI · Paper page
  157. Tieman SB 1984 Effects of monocular deprivation on geniculocortical synapses in the cat J Comp Neurol 222 166 176 10.1002/cne.902220203 6699206 · DOI · Paper page
  158. Todd KJ Darabid H Robitaille R 2010 Perisynaptic glia discriminate patterns of motor nerve activity and influence plasticity at the neuromuscular junction J Neurosci 30 11870 11882 10.1523/JNEUROSCI.3165-10.2010 20810906 PMC6633406 · DOI
  159. Torborg CL Feller MB 2005 Spontaneous patterned retinal activity and the refinement of retinal projections Prog Neurobiol 76 213 235 10.1016/j.pneurobio.2005.09.002 16280194 · DOI
  160. Torborg CL Hansen KA Feller MB 2005 High frequency, synchronized bursting drives eye-specific segregation of retinogeniculate projections Nat Neurosci 8 72 78 10.1038/nn1376 15608630 PMC1463890 · DOI
  161. Trachtenberg JT Chen BE Knott GW Feng G Sanes JR Welker E Svoboda K 2002 Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex Nature 420 788 794 10.1038/nature01273 12490942 · DOI · Paper page
  162. Tsai PT Hull C Chu Y Greene-Colozzi E Sadowski AR Leech JM Steinberg J Crawley JN Regehr WG Sahin M 2012 Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice Nature 488 647 651 10.1038/nature11310 22763451 PMC3615424 · DOI · Paper page
  163. Tsvetkov AS Miller J Arrasate M Wong JS Pleiss MA Finkbeiner S 2010 A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model Proc Natl Acad Sci USA 107 16982 16987 10.1073/pnas.1004498107 20833817 PMC2947884 · DOI · Paper page
  164. Turney SG Lichtman JW 2012 Reversing the outcome of synapse elimination at developing neuromuscular junctions in vivo: evidence for synaptic competition and its mechanism PLoS Biol 10 e1001352 10.1371/journal.pbio.1001352 22745601 PMC3383738 · DOI
  165. Uesaka N Uchigashima M Mikuni T Nakazawa T Nakao H Hirai H Aiba A Watanabe M Kano M 2014 Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain Science (80-) 344 1020 1023 10.1126/science.1252514 24831527 · DOI
  166. Umemori H Sanes JR 2008 Signal regulatory proteins (SIRPS) are secreted presynaptic organizing molecules J Biol Chem 283 34053 34061 10.1074/jbc.M805729200 18819922 PMC2662226 · DOI
  167. Urbano FJ Rosato-Siri MD Uchitel OD 2002 Calcium channels involved in neurotransmitter release at adult, neonatal and P/Q-type deficient neuromuscular junctions (Review) Mol Membr Biol 19 293 300 10.1080/0968768021000035087 12512776 · DOI
  168. Van Slegtenhorst M de Hoogt R Hermans C Nellist M Janssen B Verhoef S Lindhout D van den Ouweland A Halley D Young J Burley M Jeremiah S Woodward K Nahmias J Fox M Ekong R Osborne J Wolfe J Povey S Snell RG Cheadle JP Jones AC Tachataki M Ravine D Sampson JR Reeve MP Richardson P Wilmer F Munro C Hawkins TL Sepp T Ali JB Ward S Green AJ Yates JR Kwiatkowska J Henske EP Short MP Haines JH Jozwiak S Kwiatkowski DJ 1997 Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34 Science (80-) 277 805 808 9242607
  169. Vaughn JE 1989 Fine structure of synaptogenesis in the vertebrate central nervous system Synapse 3 255 285 10.1002/syn.890030312 2655146 · DOI
  170. Vuong HE Hsiao EY 2017 Emerging roles for the gut microbiome in autism spectrum disorder Biol Psychiatry 81 411 423 10.1016/j.biopsych.2016.08.024 27773355 PMC5285286 · DOI · Paper page
  171. Walsh MK Lichtman JW 2003 In vivo time-lapse imaging of synaptic takeover associated with naturally occurring synapse elimination Neuron 37 67 73 10.1016/S0896-6273(02)01142-X 12526773 · DOI
  172. Wang Zheng Miao G Xue X Guo X Yuan C Wang Zhaoyu Zhang G Chen Y Feng D Hu J Zhang H 2016 The Vici Syndrome Protein EPG5 Is a Rab7 Effector that Determines the Fusion Specificity of Autophagosomes with Late Endosomes/Lysosomes Mol Cell 63 781 795 10.1016/j.molcel.2016.08.021 27588602 · DOI · Paper page
  173. Weeber EJ Levy M Sampson MJ Anflous K Armstrong DL Brown SE Sweatt JD Craigen WJ 2002 The role of mitochondrial porins and the permeability transition pore in learning and synaptic plasticity J Biol Chem 277 18891 18897 10.1074/jbc.M201649200 11907043 · DOI
  174. Wei H Li Y Han S Liu S Zhang N Zhao L Li S Li J 2016 cPKCγ-Modulated Autophagy in Neurons Alleviates Ischemic Injury in Brain of Mice with Ischemic Stroke Through Akt-mTOR Pathway Transl Stroke Res 7 497 511 10.1007/s12975-016-0484-4 27510769 · DOI
  175. Wong-Riley MT Welt C 1980 Histochemical changes in cytochrome oxidase of cortical barrels after vibrissal removal in neonatal and adult mice Proc Natl Acad Sci USA 77 2333 2337 6246540 PMC348709
  176. Xie ZP Poo MM 1986 Initial events in the formation of neuromuscular synapse: rapid induction of acetylcholine release from embryonic neuron Proc Natl Acad Sci USA 83 7069 7073 3462745 PMC386654
  177. Yang G Pan F Gan WB 2009 Stably maintained dendritic spines are associated with lifelong memories Nature 462 920 924 10.1038/nature08577 19946265 PMC4724802 · DOI · Paper page
  178. Yang JF Cao G Koirala S Reddy LV Ko CP 2001 Schwann cells express active agrin and enhance aggregation of acetylcholine receptors on muscle fibers J Neurosci 21 9572 9584 11739568 PMC6763019
  179. Yazdani U Terman JR 2006 The semaphorins Genome Biol 7 211 10.1186/gb-2006-7-3-211 16584533 PMC1557745 · DOI
  180. Yuste R 2013 Electrical compartmentalization in dendritic spines Annu Rev Neurosci 36 429 449 10.1146/annurev-neuro-062111-150455 23724997 · DOI · Paper page
  181. Yuste R 2015 The discovery of dendritic spines by Cajal Front Neuroanat 9 18 10.3389/fnana.2015.00018 25954162 PMC4404913 · DOI
  182. Yuste R Bonhoeffer T 2004 Genesis of dendritic spines: insights from ultrastructural and imaging studies Nat Rev Neurosci 5 24 34 10.1038/nrn1300 14708001 · DOI
  183. Yuste R Denk W 1995 Dendritic spines as basic functional units of neuronal integration Nature 375 682 684 10.1038/375682a0 7791901 · DOI · Paper page
  184. Zhang H Cicchetti G Onda H Koon HB Asrican K Bajraszewski N Vazquez F Carpenter CL Kwiatkowski DJ 2003 Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR J Clin Invest 112 1223 1233 10.1172/JCI17222 14561707 PMC213485 · DOI
  185. Ziburkus J Dilger EK Lo FS Guido W 2009 LTD and LTP at the developing retinogeniculate synapse J Neurophysiol 102 3082 3090 10.1152/jn.90618.2008 19776360 PMC2804430 · DOI
  186. Ziv NE Smith SJ 1996 Evidence for a role of dendritic filopodia in synaptogenesis and spine formation Neuron 17 91 102 10.1016/S0896-6273(00)80283-4 8755481 · DOI

Cited by

Sorted by citations

Authors
Lieberman, O. J., McGuirt, A. F., Tang, G., & Sulzer, D.
Affiliations
Columbia University Irving Medical Center (US)
Corresponding author
Sulzer, David
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2019-02
Volume
122
Pages
49-63
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2018.04.017
PMC
PMC6204314
OpenAlex
W2802189643
Cited by
87
References
30
Citations by year
2026: 5 · 2025: 11 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 13 · 2020: 19 · 2019: 6 · 2018: 4
FWCI
1.38
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NIMH (F30MH114390)
  • Simons
  • JPB
  • Parkinson's Foundations and NIDA (R01 DA007418)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
autophagy, synaptic pruning, dendritic spines, excitatory synapses, glial cells, brain development, neurodevelopmental disorders, postnatal development, adolescence, learning and memory
MeSH terms
Animals, Autophagy, Central Nervous System, Humans, Neuroglia, Neurons, Synapses

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review