CoChat
Sign Up
Cited by 133Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

Regulation of spine and synapse formation by activity-dependent intracellular signaling pathways

Open access
Saneyoshi, Takeo, Fortin, Dale A, Soderling, Thomas R·2010·Current Opinion in Neurobiology
DOI 10.1016/j.conb.2009.09.013PMC PMC2856474
Open this paper in CoChat — free account

Abstract

Formation of the human brain during embryonic and postnatal development is an extraordinarily complex process resulting at maturity in billions of neurons with trillions of specialized connections called synapses. These synapses, composed of a varicosity or bouton from a presynaptic neuron that communicates with a dendritic spine of the postsynaptic neuron, comprise the neural network that is essential for complex behavioral phenomena and cognition. Inappropriate synapse formation or structure is thought to underlie several developmental neuropathologies. Even in the mature CNS, alterations in synapse structure and function continues to be a very dynamic process that is foundational to learning and memory as well as other adaptive abilities of the brain. This synaptic plasticity in mature neurons, which is often triggered by certain patterns of neural activity, is again multifaceted and involves post-translational modifications (e.g. phosphorylation) and subcellular relocalization or trafficking (endocytosis/exocytosis) of existing synaptic proteins, initiation of protein synthesis from existing mRNAs localized in dendrites or spines, and triggering of new gene transcription in the nucleus. These various cellular processes support varying temporal components of synaptic plasticity that begin within 1-2 min but can persist for hours to days. This review will give a critical assessment of activity-dependent molecular modulations of synapses reported over the past couple years. Owing to space limitations, it will focus on mammalian excitatory (i.e. glutamatergic) synapses and will not consider several activity-independent signaling pathways (e.g. ephrinB receptor) that also modulate spine and synapse formation.

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.conb.2009.09.013

Cites

9 of 9 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?

  • Downstream of CaMKII, Ras and Rho GTPases are important for regulating spine morphology and synaptic strength.

    “Downstream of CaMKII, Ras and Rho GTPases are important for regulating spine morphology (Ramakers, 2002; Saneyoshi et al., 2010) and synaptic strength (Zhu et al., 2002; Patterson et al., 2010).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Saneyoshi et al., 2010

    In “Regulation of spine and synapse formation by small GTPases” (page not provided), the review links CaMKII to Rac-regulating proteins involved in spine maturation and formation, and identifies Rho-family GTPases as regulators of spine morphology. It discusses Ras in relation to AMPA-receptor trafficking, but does not establish Ras as downstream of CaMKII in regulating spine morphology. The citing sentence attaches Saneyoshi et al. to spine morphology, not synaptic strength. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Rho GTPases play important roles in regulating the actin cytoskeleton, which is essential for spine-specific, long-term structural and functional plasticity.

    “Rho GTPases may constitute such signalling, because they play important roles in regulating actin cytoskeleton3,16, which is essential for spine-specific, long-term structural and functional plasticity14,17.”

    From Local, persistent activation of Rho GTPases during plasticity of single dendritic spines (2011) · cites this paper as [3]

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

Flagged first, then by citations

Research works printed but not linked: 64

  1. [1]Essmann CL Martinez E Geiger JC Zimmer M Traut MH Stein V Klein R Acker-Palmer A Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors Nat Neurosci 2008 11 1035 1043 19160501
  2. [2]Tolias KF Bikoff JB Kane CG Tolias CS Hu L Greenberg ME The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development Proc Natl Acad Sci USA 2007 104 7265 7270 17440041 PMC1855368
  3. [3]Cingolani LA Goda Y Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy Nat Rev Neurosci 2008 9 344 356 18425089
  4. [4]Spitzer NC Electrical activity in early neuronal development Nature 2006 444 707 712 17151658
  5. [5]Lang SB Stein V Bonhoeffer T Lohmann C Endogenous brain-derived neurotrophic factor triggers fast calcium transients at synapses in developing dendrites J Neurosci 2007 27 1097 1105 17267564 PMC6673203
  6. [6]Wayman GA Lee YS Tokumitsu H Silva A Soderling TR Calmodulin-kinases: modulators of neuronal development and plasticity Neuron 2008 59 914 931 18817731 PMC2664743
  7. [8]Ma XM Kiraly DD Gaier ED Wang Y Kim EJ Levine ES Eipper BA Mains RE Kalirin-7 is required for synaptic structure and function J Neurosci 2008 28 12368 12382 19020030 PMC2586970
  8. [9]Tolias KF Bikoff JB Burette A Paradis S Harrar D Tavazoie S Weinberg RJ Greenberg ME The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines Neuron 2005 45 525 538 15721239
  9. [10]Davare MA Fortin DA Saneyoshi T Nygaard S Kaech S Banker G Soderling TR Wayman GA Transient receptor potential canonical 5 channels activate Ca2+/calmodulin kinase Igamma to promote axon formation in hippocampal neurons J Neurosci 2009 29 9794 9808 19657032 PMC2763510
  10. [11]Wayman GA Kaech S Grant WF Davare M Impey S Tokumitsu H Nozaki N Banker G Soderling TR Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I J Neurosci 2004 24 3786 3794 15084659 PMC6729350
  11. Saneyoshi T Wayman G Fortin D Davare M Hoshi N Nozaki N Natsume T Soderling TR Activity-dependent synaptogenesis: regulation by a CaM- kinase kinase/CaM-kinase I/betaPIX signaling complex Neuron 2008 57 94 107 This study demonstrates that phosphorylation of the RacGEF betaPIX by CaMKK/CaMKI in a signaling complex with GIT1 regulates Rac1 and activity-dependent synaptogenesis 18184567 PMC2277504
  12. [14]Schmitt JM Guire ES Saneyoshi T Soderling TR Calmodulin-dependent kinase kinase/calmodulin kinase I activity gates extracellular-regulated kinase-dependent long-term potentiation J Neurosci 2005 25 1281 1290 15689566 PMC6725957
  13. Vo N Klein ME Varlamova O Keller DM Yamamoto T Goodman RH Impey S A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis Proc Natl Acad Sci USA 2005 102 16426 16431 This was the first study to provide a mechanism by which microRNAs can regulate neuronal development 16260724 PMC1283476
  14. [16]Wayman GA Davare M Ando H Fortin D Varlamova O Cheng HY Marks D Obrietan K Soderling TR Goodman RH An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP Proc Natl Acad Sci USA 2008 105 9093 9098 18577589 PMC2449370
  15. [17]Nakazawa T Kuriu T Tezuka T Umemori H Okabe S Yamamoto T Regulation of dendritic spine morphology by an NMDA receptor-associated Rho GTPase-activating protein, p250GAP J Neurochem 2008 105 1384 1393 18331582
  16. [18]Govek EE Newey SE Van Aelst L The role of the Rho GTPases in neuronal development Genes Dev 2005 19 1 49 15630019
  17. [19]Zhang H Macara IG The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase Dev Cell 2008 14 216 226 18267090 PMC2768076
  18. [20]Derkach VA Oh MC Guire ES Soderling TR Regulatory mechanisms of AMPA receptors in synaptic plasticity Nat Rev Neurosci 2007 8 101 113 17237803
  19. [21]Shepherd JD Huganir RL The cell biology of synaptic plasticity: AMPA receptor trafficking Annu Rev Cell Dev Biol 2007 23 613 643 17506699
  20. [23]Li Z Aizenman CD Cline HT Regulation of rho GTPases by crosstalk and neuronal activity in vivo Neuron 2002 33 741 750 11879651
  21. [24]Ryan XP Alldritt J Svenningsson P Allen PB Wu GY Nairn AC Greengard P The Rho-specific GEF Lfc interacts with neurabin and spinophilin to regulate dendritic spine morphology Neuron 2005 47 85 100 15996550
  22. [25]Qin Y Zhu Y Baumgart JP Stornetta RL Seidenman K Mack V van Aelst L Zhu JJ State-dependent Ras signaling and AMPA receptor trafficking Genes Dev 2005 19 2000 2015 16107614 PMC1199571
  23. [26]Harvey CD Yasuda R Zhong H Svoboda K The spread of Ras activity triggered by activation of a single dendritic spine Science 2008 321 136 140 18556515 PMC2745709
  24. [27]Govek EE Newey SE Akerman CJ Cross JR Van der Veken L Van Aelst L The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis Nat Neurosci 2004 7 364 372 15034583
  25. Nadif Kasri N Nakano-Kobayashi A Malinow R Li B Van Aelst L The Rho-Rho-linked mental retardation protein oligophrenin-1 controls synapse maturation and plasticity by stabilizing AMPA receptors Genes Dev 2009 23 1289 1302 This study is the first to provide a mechanism, Rho regulation of AMPAR dynamics, by which genetic deficits in oligophrenin-1 are linked to abnormal synaptic development and glutamatergic dysfunction 19487570 PMC2701582
  26. Kang R Wan J Arstikaitis P Takahashi H Huang K Bailey AO Thompson JX Roth AF Drisdel RC Mastro R Neural palmitoyl-proteomics reveals dynamic synaptic palmitoylation Nature 2008 456 904 909 The authors present a novel method to isolate neural palmitoylated proteins and describe the mechanism by which Cdc42 regulates synaptogenesis through palmitoyl modification 19092927 PMC2610860
  27. [30]Costa-Mattioli M Sossin WS Klann E Sonenberg N Translational control of long-lasting synaptic plasticity and memory Neuron 2009 61 10 26 19146809 PMC5154738
  28. [31]Klein ME Impey S Goodman RH Role reversal: the regulation of neuronal gene expression by microRNAs Curr Opin Neurobiol 2005 15 507 513 16150590
  29. [32]Kosik KS The neuronal microRNA system Nat Rev Neurosci 2006 7 911 920 17115073
  30. [33]Smalheiser NR Lugli G microRNA regulation of synaptic plasticity Neuromol Med 2009 PMC3732454 19458942
  31. [34]Davis TH Cuellar TL Koch SM Barker AJ Harfe BD McManus MT Ullian EM Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus J Neurosci 2008 28 4322 4330 18434510 PMC3844796
  32. [35]Schratt GM Tuebing F Nigh EA Kane CG Sabatini ME Kiebler M Greenberg ME A brain-specific microRNA regulates dendritic spine development Nature 2006 439 283 289 16421561
  33. [36]Siegel G Obernosterer G Fiore R Oehmen M Bicker S Christensen M Khudayberdiev S Leuschner PF Busch CJ Kane C A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis Nat Cell Biol 2009 11 705 716 19465924 PMC3595613
  34. [37]Schratt G Fine-tuning neural gene expression with microRNAs Curr Opin Neurobiol 2009 19 213 219 19539460
  35. [38]Turrigiano GG The self-tuning neuron: synaptic scaling of excitatory synapses Cell 2008 135 422 435 18984155 PMC2834419
  36. [40]Lee SJ Escobedo-Lozoya Y Szatmari EM Yasuda R Activation of CaMKII in single dendritic spines during long-term potentiation Nature 2009 458 299 304 19295602 PMC2719773
  37. Steiner P Higley MJ Xu W Czervionke BL Malenka RC Sabatini BL Destabilization of the postsynaptic density by PSD-95 serine 73 phosphorylation inhibits spine growth and synaptic plasticity Neuron 2008 60 788 802 Demonstrates CaMKII phosphorylation of PSD95 at S73 triggers the termination of spine expansion by displacing PSD95 and SHANK2 from previously activated spines 19081375 PMC2671083
  38. [43]Hayashi MK Tang C Verpelli C Narayanan R Stearns MH Xu RM Li H Sala C Hayashi Y The postsynaptic density proteins Homer and Shank form a polymeric network structure Cell 2009 137 159 171 19345194 PMC2680917
  39. [44]Sala C Piech V Wilson NR Passafaro M Liu G Sheng M Regulation of dendritic spine morphology and synaptic function by Shank and Homer Neuron 2001 31 115 130 11498055
  40. [45]Park M Salgado JM Ostroff L Helton TD Robinson CG Harris KM Ehlers MD Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes Neuron 2006 52 817 830 17145503 PMC1899130
  41. [47]Petrini EM Lu J Cognet L Lounis B Ehlers MD Choquet D Endocytic trafficking and recycling maintain a pool of mobile surface AMPA receptors required for synaptic potentiation Neuron 2009 63 92 105 19607795 PMC2847611
  42. [48]Heine M Groc L Frischknecht R Beique JC Lounis B Rumbaugh G Huganir RL Cognet L Choquet D Surface mobility of postsynaptic AMPARs tunes synaptic transmission Science 2008 320 201 205 18403705 PMC2715948
  43. [49]Correia SS Bassani S Brown TC Lise MF Backos DS El-Husseini A Passafaro M Esteban JA Motor protein-dependent transport of AMPA receptors into spines during long-term potentiation Nat Neurosci 2008 11 457 466 18311135
  44. Wang Z Edwards JG Riley N Provance DW Jr Karcher R Li XD Davison IG Ikebe M Mercer JA Kauer JA Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity Cell 2008 135 535 548 Demonstrates that NMDA-dependent plasticity induces Myosin Vb association with recycling endosomes and subsequent trafficking of GluR1 into spines 18984164 PMC2585749
  45. [51]Gabe Lee MT Mishra A Lambright DG Structuralmechanisms for regulation of membrane traffic by Rab GTPases Traffic 2009 PMC4784978 19522756
  46. [52]Brown TC Correia SS Petrok CN Esteban JA Functional compartmentalization of endosomal trafficking for the synaptic delivery of AMPA receptors during long-term potentiation J Neurosci 2007 27 13311 13315 18045925 PMC6673392
  47. [53]Plant K Pelkey KA Bortolotto ZA Morita D Terashima A McBain CJ Collingridge GL Isaac JT Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation Nat Neurosci 2006 9 602 604 16582904
  48. [54]Guire ES Oh MC Soderling TR Derkach VA Recruitment of calcium-permeable AMPA receptors during synaptic potentiation is regulated by CaM-kinase I J Neurosci 2008 28 6000 6009 18524905 PMC2671029
  49. [55]Adesnik H Nicoll RA Conservation of glutamate receptor 2-containing AMPA receptors during long-term potentiation J Neurosci 2007 27 4598 4602 17460072 PMC6672988
  50. [56]Gray EE Fink AE Sarinana J Vissel B O’Dell TJ Long-term potentiation in the hippocampal CA1 region does not require insertion and activation of GluR2-lacking AMPA receptors J Neurophysiol 2007 98 2488 2492 17652419
  51. [57]Kwak S Weiss JH Calcium-permeable AMPA channels in neurodegenerative disease and ischemia Curr Opin Neurobiol 2006 16 281 287 16698262
  52. [58]Liu SJ Zukin RS Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death Trends Neurosci 2007 30 126 134 17275103
  53. [59]Kopec CD Real E Kessels HW Malinow R GluR1 links structural and functional plasticity at excitatory synapses J Neurosci 2007 27 13706 13718 18077682 PMC6673607
  54. [60]Osterweil E Wells DG Mooseker MS A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis J Cell Biol 2005 168 329 338 15657400 PMC2171578
  55. [62]Sbai O Ferhat L Bernard A Gueye Y Ould-Yahoui A Thiolloy S Charrat E Charton G Tremblay E Risso JJ Vesicular trafficking and secretion of matrix metalloproteinases-2, -9 and tissue inhibitor of metalloproteinases-1 in neuronal cells Mol Cell Neurosci 2008 39 549 568 18817873
  56. [63]Schnell E Nicoll RA Hippocampal synaptic transmission and plasticity are preserved in myosin Va mutant mice J Neurophysiol 2001 85 1498 1501 11287473
  57. [64]Sellers JR Thirumurugan K Sakamoto T Hammer JA 3rd Knight PJ Calcium and cargoes as regulators of myosin 5a activity Biochem Biophys Res Commun 2008 369 176 181 18060865
  58. [65]Wu X Sakamoto T Zhang F Sellers JR Hammer JA 3rd In vitro reconstitution of a transport complex containing Rab27a, melanophilin and myosin Va FEBS Lett 2006 580 5863 5868 17045265
  59. [66]Nagerl UV Eberhorn N Cambridge SB Bonhoeffer T Bidirectional activity-dependent morphological plasticity in hippocampal neurons Neuron 2004 44 759 767 15572108
  60. Sdrulla AD Linden DJ Double dissociation between long-term depression and dendritic spine morphology in cerebellar Purkinje cells Nat Neurosci 2007 10 546 548 Demonstrates that electrical or chemical LTD of identified parallel fiber–Purkinje cell synapses is not associated with structural changes in dendritic spines 17435753
  61. [69]Wang XB Yang Y Zhou Q Independent expression of synaptic and morphological plasticity associated with long-term depression J Neurosci 2007 27 12419 12429 17989307 PMC6673249
  62. Bastrikova N Gardner GA Reece JM Jeromin A Dudek SM Synapse elimination accompanies functional plasticity in hippocampal neurons Proc Natl Acad Sci USA 2008 105 3123 3127 Used virally infected CA1 and CA3 neurons to visualize coupled pre- and postsynaptic structures and found that LTD induced presynaptic terminal withdrawal from coupled dendritic spines 18287055 PMC2268595
  63. [71]Becker N Wierenga CJ Fonseca R Bonhoeffer T Nagerl UV LTD induction causes morphological changes of presynaptic boutons and reduces their contacts with spines Neuron 2008 60 590 597 19038217
  64. [72]Richter JD Klann E Making synaptic plasticity and memory last: mechanisms of translational regulation Genes Dev 2009 23 1 11 19136621

Cited by

Sorted by citations

Authors
Saneyoshi, T., Fortin, D. A., & Soderling, T. R.
Affiliations
  • RIKEN Center for Brain Science (JP)
  • Oregon Health & Science University (US)
Corresponding author
Soderling, Thomas R
ORCID
Saneyoshi, Takeo
Venue
Current Opinion in Neurobiology
Publisher
Elsevier BV
Published
2010-02
Volume
20
Issue
1
Pages
108-115
ISSN
0959-4388 (ISSN-L)
DOI
10.1016/j.conb.2009.09.013
PMC
PMC2856474
OpenAlex
W2019203795
Cited by
133
References
9
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 1 · 2017: 7 · 2016: 9 · 2015: 5 · 2014: 17 · 2013: 16 · 2012: 15
FWCI
1.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM041292)
  • National Institute of Neurological Disorders and Stroke (R01NS027037)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
dendritic spine formation, synaptogenesis, activity-dependent signaling, synaptic plasticity, excitatory synapses, glutamatergic synapses, post-translational modification, protein trafficking, brain development
MeSH terms
Animals, Humans, Nerve Net, Synaptic Transmission, Neuronal Plasticity, Neurons, Synapses, Signal Transduction, Dendritic Spines

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