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Cited by 322Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeural dynamics and brain function

Experience-dependent structural plasticity in the cortex

Open access
Fu, Min, Zuo, Yi·2011·Trends in Neurosciences
DOI 10.1016/j.tins.2011.02.001PMC PMC3073830
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Abstract

Synapses are the fundamental units of neuronal circuits. Synaptic plasticity can occur through changes in synaptic strength, as well as through the addition/removal of synapses. Two-photon microscopy in combination with fluorescence labeling offers a powerful tool to peek into the living brain and follow structural reorganization at individual synapses. Time-lapse imaging depicts a dynamic picture in which experience-dependent plasticity of synaptic structures varies between different cortical regions and layers, as well as between neuronal subtypes. Recent studies have demonstrated that the formation and elimination of synaptic structures happens rapidly in a subpopulation of cortical neurons during various sensorimotor learning experiences, and that stabilized synaptic structures are associated with long lasting memories for the task. Therefore, circuit plasticity, mediated by structural remodeling, provides an underlying mechanism for learning and memory.

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Written from the paper’s full text.

TL;DR

This review synthesizes in vivo two-photon imaging evidence that cortical synaptic structures are remodeled by experience, with rapid spine formation and elimination in subsets of neurons and stabilization linked to lasting memory. It argues that structural circuit rewiring complements synaptic strength changes in learning, while noting unresolved questions about deep layers, cell-type specificity, and causality.

Key findings

  • Dendritic spines are highly dynamic early and then stabilize: filopodia fall from over 50% at 2 weeks to under 10% at 1 month and 2–3% in adult barrel cortex; roughly 30% of spines are pruned between 1 and 4 months; more than 70% of adult spines remain stable over 18 months.
  • Experience changes spine dynamics: monocular deprivation increases spine formation and density selectively on L5 apical dendrites, and many new spines persist after binocular vision is restored; later deprivation enlarges these spines rather than adding more. Motor training induces new spines within one hour, learning acquisition correlates with spine formation, and skill maintenance correlates with survival of new spines, which can persist up to 4 months.
  • Plasticity differs by cell type and region: L5 pyramidal neurons with complex apical tufts preferentially gain new spines; inhibitory interneuron dendrites are dynamic in superficial L2/3, with visual deprivation increasing dynamic branches about 3-fold and producing roughly 10% interneuron synapse turnover per week. Axonal boutons also differ, with thalamocortical boutons about 85% stable over a month versus about 60% turnover in L6 cortical axons, and about 7% weekly bouton turnover in adult monkey visual cortex.
  • Structural changes likely correspond to functional synapses: EM and electrophysiology evidence indicates that persistent new spines and many boutons have synaptic contacts, although direct causal proof is still lacking.

Methods

  • Narrative review of in vivo structural imaging studies, primarily using two-photon laser scanning microscopy with fluorescent labeling such as thy1 transgenic mice and viral EGFP.
  • Covers excitatory pyramidal neurons, inhibitory interneurons, and axons across development and adulthood, including sensory manipulation, motor learning, songbird learning, stroke, neurodegeneration, and Fragile X Syndrome.
  • Synthesizes findings on spine, filopodium, and bouton turnover, morphology, stability, and links to functional synaptic connectivity; no primary data or meta-analysis are presented.

Limitations

  • Stated: current two-photon imaging is mostly limited to superficial cortical layers, mainly L1 and L2, leaving deeper-layer plasticity unclear; thy1 lines label sparse and often mixed cell populations, limiting cell-type-specific imaging; most learning studies show correlation rather than causation between structural dynamics and behavior.
  • Stated: the field debates whether dendritic protrusions should be classified as spines versus filopodia and what baseline spine dynamics actually are; discrepancies may come from mouse lines, animal age, cranial window versus thin skull preparation, analysis methods, and imaging intervals.
  • Evident: as a review, it lacks a systematic search or quantitative synthesis, and many conclusions rest on heterogeneous protocols and indirect structural proxies for synaptic connectivity.

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Integrity signals

Registry

Crossref · 10.1016/j.tins.2011.02.001

Cites

97 of 97 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 160 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Experience modifies neuronal connections by selectively stabilizing some synapses and removing others.

    “Experience modifies these connections by selectively stabilizing some synapses and removing others [8, 12, 13].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [8] Holtmaat A Svoboda K 2009 Experience-dependent structural synaptic plasticity in the mammalian brain Nat Rev Neurosci 10 647 658 19693029 source

      Not checked in the free run.

    • cites [12] Lichtman JW Colman H 2000 Synapse elimination and indelible memory Neuron 25 269 278 10719884 source

      Not checked in the free run.

    • cites [13] Draft RW Lichtman JW 2009 It’s lonely at the top: winning climbing fibers ascend dendrites solo Neuron 63 6 8 19607787 PMC2790139 source

      Not checked in the free run.

  • Premisecitation

    Mice lacking δ-catenin show progressive dendritic retraction and spine loss after 5 weeks of age.

    “Recent in vivo studies show that mutant mice lacking the cell adhesion molecule, δ-catenin, undergo progressive retraction of dendrites and spine loss after 5 weeks of age [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Matter C 2009 Delta-catenin is required for the maintenance of neural structure and function in mature cortex in vivo Neuron 64 320 327 19914181 PMC2840037 source

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  • Interpretationcitation

    Because filopodia are rare in adult animals, conclusions about adult spine dynamics are largely unaffected by whether filopodia are included or excluded.

    “Given the fact that filopodia are rare in adults, conclusions of adult spine dynamics are largely not affected by including or excluding filopodia from the analyses.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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  • Premisecitation

    Cortical pyramidal neuron dendritic branches are mostly stable in adulthood, apart from small tip extensions and retractions.

    “In vivo imaging of cortical pyramidal neurons has shown that, except for small tip extensions and retractions, dendritic branches are mostly stable in adulthood [19, 20].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] Trachtenberg JT 2002 Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex Nature 420 788 794 12490942 source

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    • cites [20] Mizrahi A Katz LC 2003 Dendritic stability in the adult olfactory bulb Nat Neurosci 6 1201 1207 14528309 source

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  • Premisecitation

    Both recent studies found a significant increase in spine turnover in the barrel cortex of Fmr1 knockout mice.

    “Both studies reveal a significant increase in spine turnover in the barrel cortex of Fmr1 KO mice.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [75] Cruz-Martin A 2010 Delayed stabilization of dendritic spines in fragile X mice J Neurosci 30 7793 7803 20534828 PMC2903441 source

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    • cites [76] Pan F 2010 Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome Proc Natl Acad Sci U S A 107 17768 17773 20861447 PMC2955121 source

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  • May combine two claims. 46
  • Classified as probably not a substantial claim. 7

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    Interpretationreasoning

    Development, experience, and various pathologies all substantially affect spine and filopodium dynamics.

    “The cumulative results from these in vivo studies reveal that development, experience, and various pathologies all affect spine and filopodium dynamics in significant ways”
    Quote in the paperSubstantial claim

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    Premisecitation

    Experience-dependent plasticity occurs in adulthood, and mammalian neuronal circuits can change in response to new experience throughout life.

    “Cumulative data have shown that experience-dependent plasticity occurs in adulthood and it is now well accepted that neuronal circuits of the mammalian brain are capable of changing in response to new experience throughout life [7–11].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [7] Zito K Svoboda K 2002 Activity-dependent synaptogenesis in the adult Mammalian cortex Neuron 35 1015 1017 12354392 source

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    • cites [8] Holtmaat A Svoboda K 2009 Experience-dependent structural synaptic plasticity in the mammalian brain Nat Rev Neurosci 10 647 658 19693029 source

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    • cites [9] Bavelier D 2010 Removing brakes on adult brain plasticity: from molecular to behavioral interventions J Neurosci 30 14964 14971 21068299 PMC2992973 source

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    • cites [10] Chen JL Nedivi E 2010 Neuronal structural remodeling: is it all about access? Curr Opin Neurobiol 20 557 562 20621466 PMC2946477 source

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    • cites [11] Yu X Zuo Y 2010 Spine plasticity in the motor cortex Curr Opin Neurobiol 10.1016/j.conb.2010.07.010 PMC2991530 20728341

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

    Premisecitation

    A functional mature neuronal circuit is formed from an initial pool of less precise synaptic connections.

    “It is generally believed that a functional, mature neuronal circuit is formed from an initial pool of less precise synaptic connections.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Holtmaat A Svoboda K 2009 Experience-dependent structural synaptic plasticity in the mammalian brain Nat Rev Neurosci 10 647 658 19693029 source

      Not checked in the free run.

    • cites [12] Lichtman JW Colman H 2000 Synapse elimination and indelible memory Neuron 25 269 278 10719884 source

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    • cites [13] Draft RW Lichtman JW 2009 It’s lonely at the top: winning climbing fibers ascend dendrites solo Neuron 63 6 8 19607787 PMC2790139 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the adult brain, synaptic plasticity continues through changes in synaptic strength and through synapse formation and elimination.

    “In the adult brain, synaptic plasticity continues through modifications of synaptic strength, as well as through formation and elimination of synapses [8, 10].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [8] Holtmaat A Svoboda K 2009 Experience-dependent structural synaptic plasticity in the mammalian brain Nat Rev Neurosci 10 647 658 19693029 source

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    • cites [10] Chen JL Nedivi E 2010 Neuronal structural remodeling: is it all about access? Curr Opin Neurobiol 20 557 562 20621466 PMC2946477 source

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    Premisecitation

    Loss of PTEN causes continuous growth of L2/3 pyramidal neuron apical dendrites and expansion of the mature cortex.

    “In contrast, absence of the tumor suppressor protein, phosphatase and tensin homolog (PTEN), results in continuous growth of L2/3 pyramidal neuron apical dendrites and expansion of the mature cortex [22].”
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    • cites [22] Chow DK 2009 Laminar and compartmental regulation of dendritic growth in mature cortex Nat Neurosci 12 116 118 19151711 PMC2842592 source

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    Premisecitation

    Ischemic stroke causes rapid spine loss and dendritic distortion within minutes, which can be mostly recovered if reperfusion occurs within one hour.

    “Ischemic stroke causes a rapid (within minutes) loss of spines and distortion of dendrites, which can be mostly recovered if reperfusion happens within one hour [67–69].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [67] Zhang S 2005 Rapid reversible changes in dendritic spine structure in vivo gated by the degree of ischemia J Neurosci 25 5333 5338 15930381 PMC6724996 source

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    • cites [68] Zhang S Murphy TH 2007 Imaging the impact of cortical microcirculation on synaptic structure and sensory-evoked hemodynamic responses in vivo PLoS Biol 5 e119 17456007 PMC1854912 source

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    • cites [69] Murphy TH 2008 Two-photon imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines J Neurosci 28 1756 1772 18272696 PMC6671530 source

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    Premisecitation

    Dendritic protrusion density changes during development and differs among neuron types.

    “Not only are these protrusions heterogeneous in shape [23–25], their density also changes during development and varies among different types of neurons [26–28].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [26] Nimchinsky EA 2002 Structure and function of dendritic spines Annu Rev Physiol 64 313 353 11826272 source

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    • cites [27] Zuo Y 2005 Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex Nature 436 261 265 16015331 source

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    • cites [28] Holtmaat AJ 2005 Transient and persistent dendritic spines in the neocortex in vivo Neuron 45 279 291 15664179 source

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    Premisecitation

    After stroke, dendritic branch remodeling and spine formation are selectively elevated in the peri-infarct area, leading to gradual recovery of spine density between 1 and 6 weeks.

    “Following stroke, dendritic branch remodeling and spine formation are selectively elevated in the peri-infarct area, leading to a gradual recovery of spine density between 1 and 6 weeks [70, 71].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [70] Brown CE 2007 Extensive turnover of dendritic spines and vascular remodeling in cortical tissues recovering from stroke J Neurosci 27 4101 4109 17428988 PMC6672555 source

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    • cites [71] Brown CE 2010 Longitudinal in vivo imaging reveals balanced and branch-specific remodeling of mature cortical pyramidal dendritic arbors after stroke J Cereb Blood Flow Metab 30 783 791 19920846 PMC2949167 source

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    Premisecitation

    Between 1 and 4 months of age, more spines are lost than formed in all cortical regions examined, resulting in about 30% pruning of total spines.

    “Between 1 to 4 months of age, more spines are lost than formed in all cortical regions examined, resulting in a ~30% pruning of total spines [27, 36].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Zuo Y 2005 Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex Nature 436 261 265 16015331 source

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    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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    Premisecitation

    In adults, more than 70% of spines are stable over 18 months, with comparable rates of spine formation and elimination.

    “In adults, more than 70% of spines are stable over 18 months, with comparable rates of spine formation and elimination [36, 39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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    • cites [39] Grutzendler J 2002 Long-term dendritic spine stability in the adult cortex Nature 420 812 816 12490949 source

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    Interpretationcitation

    Dendritic spines change morphology and turn over rapidly in developing animals but become much more stable in adults.

    “In summary, despite the debate on the baseline of spine dynamics (Box 2), it is now believed that dendritic spines change their morphology and turn over rapidly in developing animals but become much more stable in adults.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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    • cites [39] Grutzendler J 2002 Long-term dendritic spine stability in the adult cortex Nature 420 812 816 12490949 source

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    Premisecitation

    By one month of age, filopodia turn over daily while spines are much more stable.

    “While filopodia turn over on a daily basis, spines are much more stable [36, 39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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    • cites [39] Grutzendler J 2002 Long-term dendritic spine stability in the adult cortex Nature 420 812 816 12490949 source

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  • May combine two claims.

    Interpretationreasoning

    Because post-stroke behavioral recovery is thought to depend on surviving adjacent tissue taking over damaged tissue function, these studies provide a structural basis for functional reorganization in the peri-infarct region.

    “Since post-stroke behavioral recovery is thought to be dependent on adjacent, surviving tissues taking over the function of damaged tissues, these studies provide a structural basis for functional reorganization in the peri-infarct region.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [70] Brown CE 2007 Extensive turnover of dendritic spines and vascular remodeling in cortical tissues recovering from stroke J Neurosci 27 4101 4109 17428988 PMC6672555 source

      Not checked in the free run.

    • cites [71] Brown CE 2010 Longitudinal in vivo imaging reveals balanced and branch-specific remodeling of mature cortical pyramidal dendritic arbors after stroke J Cereb Blood Flow Metab 30 783 791 19920846 PMC2949167 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Less than 20% of newly formed spines persist for more than 2 days, indicating that spine stabilization is highly selective.

    “However, less than 20% of these newly formed spines persist for more than 2 days, suggesting that spine stabilization is a highly selective process [36].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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  • May combine two claims.

    Interpretationcitation

    Because new spines are more vulnerable to elimination and only a small fraction stabilize, the degree of spine dynamics does not necessarily increase linearly with longer imaging intervals.

    “Since new spines are more vulnerable for elimination and only a small percentage of them are stabilized over time [37, 38], the degree of spine dynamics does not necessarily increase linearly with increased imaging intervals.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

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    • cites [38] Yang G 2009 Stably maintained dendritic spines are associated with lifelong memories Nature 462 920 924 19946265 PMC4724802 source

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  • May combine two claims.

    Interpretationreasoning

    Shorter imaging intervals are biased toward transient structures, while longer intervals likely underestimate structural plasticity.

    “Therefore, while shorter time intervals are biased towards the changes of transient structures, longer time intervals are likely to underestimate the structural plasticity.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The effect of light exposure can be partially mimicked by increasing inhibitory signaling, suggesting that excitatory-inhibitory balance is important for spine maturation during development.

    “The effect of light exposure can be partially mimicked by increasing inhibitory signaling, suggesting that a balance between excitatory and inhibitory circuits plays an important role in spine maturation during development [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Tropea D 2010 Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex J Neurosci 30 11086 11095 20720116 PMC2932955 source

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    Interpretationcitation

    Excitatory-inhibitory balance is crucial for correct development of visual function during the critical period, suggesting that spine maturation and plasticity are important underlying components of functional changes in the visual pathway.

    “This in line with previous findings that found that excitatory-inhibitory balance is crucial for correct development of visual function during the critical period [45], thus suggesting that spine maturation and plasticity is an important underlying component of the functional changes that occur in the visual pathway.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Fagiolini M Hensch TK 2000 Inhibitory threshold for critical-period activation in primary visual cortex Nature 404 183 186 10724170 source

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    Premisecitation

    Monocular deprivation increases spine formation and leads to higher spine density selectively in apical dendrites of L5 neurons in the mouse binocular region.

    “In addition, monocular deprivation (MD) increases spine formation and leads to a higher spine density selectively in the apical dendrites of L5 neurons in the mouse binocular region [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Hofer SB 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 19005470 PMC6485433 source

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

    Interpretationcitation

    Inconsistency in baseline dendritic spine dynamics may be due to variation in neuronal subtypes labeled in different thy1 mouse lines.

    “Given the cell-type dependent dendrite morphology and dynamics [28–30], the inconsistency in baseline dynamics of dendritic spines could be due to variation in neuronal subtypes labeled in these two different mouse lines.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [28] Holtmaat AJ 2005 Transient and persistent dendritic spines in the neocortex in vivo Neuron 45 279 291 15664179 source

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    • cites [29] Holtmaat A 2006 Experience-dependent and cell-type-specific spine growth in the neocortex Nature 441 979 983 16791195 source

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    • cites [30] Hofer SB 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 19005470 PMC6485433 source

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    Premisecitation

    A few days of light exposure during the critical period P21-28 decreases spine motility and restores mature spine morphology.

    “A few days of light exposure during the critical period (i.e., postnatal days (P) 21–28 in mice) decreases spine motility and restores the mature spine morphology [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Tropea D 2010 Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex J Neurosci 30 11086 11095 20720116 PMC2932955 source

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    Interpretationcitation

    Because filopodia almost completely turn over daily, including or excluding them may greatly contribute to discrepancies between results.

    “Furthermore, it has been shown that filopodia almost completely turnover on a daily basis [36], thus including or excluding filopodia in the analysis may greatly contribute to the discrepancy between results.”
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    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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    Interpretationcitation

    Because dendritic spine dynamics decrease with age, comparing baselines across different ages is difficult.

    “Since the dynamics of dendritic spines [28, 36] decrease with age, it could therefore be hard to compare between different baselines.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Holtmaat AJ 2005 Transient and persistent dendritic spines in the neocortex in vivo Neuron 45 279 291 15664179 source

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    • cites [36] Zuo Y 2005 Development of long-term dendritic spine stability in diverse regions of cerebral cortex Neuron 46 181 189 15848798 source

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    Premisecitation

    During subsequent training, elimination is largely restricted to spines that existed before training, while new spines induced during learning are preferentially stabilized even up to 4 months after training stops.

    “Furthermore, elimination during subsequent training is largely restricted to spines that existed before training, while the new spines induced during learning are found to be preferentially stabilized, even long after training stops (i.e., up to 4 months) [37]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

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    Interpretationcitation

    Because distal and proximal forelimb corticospinal neurons are intermingled in rat motor cortex, structural changes during learning are restricted to discrete subsets of neurons preferentially involved in novel motor experience.

    “Given the fact that distal and proximal forelimb corticospinal neurons are intermingled within the rat motor cortex [47], this finding indicates that structural changes during learning are restricted to discrete subsets of neurons preferentially involved in novel motor experience.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Wang L 2010 Structural plasticity within highly specific neuronal populations identifies a unique parcellation of motor learning in the adult brain Proc Natl Acad Sci U S A 10.1073/pnas.1014335108 PMC3038698 21257908 source

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    Premisecitation

    In adult mice older than 4 months, sensory manipulation continues to modify spine dynamics but less robustly than in younger animals, suggesting a more rigid neuronal circuit in adults.

    “In adult mice (>4 months), sensory manipulation continues to modify spine dynamics, but less robustly than in younger animals, suggesting a more rigid neuronal circuit in adult animals [27].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Zuo Y 2005 Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex Nature 436 261 265 16015331 source

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    Premisecitation

    Subsequent monocular deprivation fails to increase spine formation but selectively enlarges spines formed during earlier monocular deprivation, suggesting that new spines bear functional synapses and are reactivated during the second deprivation.

    “Interestingly, subsequent MD fails to increase spine formation, but selectively enlarges the spines formed during earlier MD, suggesting that new spines formed during the initial MD bear functional synapses and are reactivated during the second MD [30]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Hofer SB 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 19005470 PMC6485433 source

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  • May combine two claims.

    Premisecitation

    When binocular vision is restored, spine formation returns to baseline, but spine density remains elevated and many new spines formed during monocular deprivation persist.

    “When binocular vision is restored, spine formation returns to the baseline. However, spine density remains elevated and many of the new spines formed during MD persist [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Hofer SB 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 19005470 PMC6485433 source

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  • May combine two claims.

    Premisecitation

    During early postnatal development in rats, trimming all whiskers unilaterally decreases spine and filopodium motility in the contralateral barrel cortex during P11-13, but has no effect on their density, length, or shape.

    “During early postnatal development in rats, trimming all whiskers unilaterally decreases both spine and filopodium motility in the contralateral barrel cortex during a brief time window (P11–13), but has no effect on their density, length or shape [17].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Lendvai B 2000 Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo Nature 404 876 881 10786794 source

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    Premisecitation

    This rapid spinogenesis is followed by enhanced spine elimination, resulting in overall spine density similar to that in control mice.

    “This rapid spinogenesis is followed by enhanced spine elimination, resulting in a similar overall spine density to that observed in control mice.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Subsequent training of pre-trained mice with a novel motor skill continues to induce robust spinogenesis in the adult motor cortex, indicating that different motor skills are likely encoded by different subpopulations of synapses in the motor cortex.

    “Furthermore, subsequent training of pre-trained mice with a novel motor skill continues to induce a robust spinogenesis in the adult motor cortex, indicating that different motor skills are likely encoded by different subpopulations of synapses in the motor cortex [37]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

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  • May combine two claims.

    Premisecitation

    In songbirds, spine dynamics of HVC neurons decrease with age, and song learning around P60 triggers rapid dendritic spine stabilization of HVC neurons.

    “Using a lentivirus expressing EGFP that was intracranially injected into the HVC nucleus, this study demonstrated that spine dynamics of HVC neurons decreased with age, and song learning around P60 triggered rapid dendritic spine stabilization of HVC neurons [48].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Roberts TF 2010 Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning Nature 463 948 952 20164928 PMC2918377 source

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    Premisecitation

    In adults, motor learning increases spine turnover in naïve mice but not in mice pre-trained with the same task in adolescence, suggesting that the circuit required for the task is established during adolescent training and maintained into adulthood.

    “In adults, motor learning increases spine turnover in naïve mice, but not in mice that have been trained with the same task in adolescence (pre-trained mice) [37], suggesting that the circuit required for such a task is established during adolescent training and maintained into adulthood.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Stabilized new spines outlast experiences and may serve as structural traces for earlier memories, preparing the brain for quicker adaptation to similar experiences.

    “In addition, stabilized new spines outlast experiences per se and may serve as structural traces for earlier memories, therefore preparing the brain for quicker adaptation to similar experiences in the future [30, 37].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [30] Hofer SB 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 19005470 PMC6485433 source

      Not checked in the free run.

    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A higher degree of spine turnover before song learning correlates with a greater capacity for subsequent song imitation, suggesting that structural dynamics in sensorimotor circuits may contribute to behavioral outcomes.

    “Interestingly, a higher degree of spine turnover before song learning was found to correlate with a greater capacity for subsequent song imitation, suggesting that structural dynamics in sensorimotor circuits may greatly contribute to behavioral outcomes [48]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Roberts TF 2010 Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning Nature 463 948 952 20164928 PMC2918377 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In young adult mice older than 6 weeks, dendritic branches of inhibitory interneurons in superficial cortical layers are very dynamic, unlike the stable dendritic branches of pyramidal neurons.

    “Live imaging of interneuron dendritic arbors in young adult mice (older than 6 weeks) demonstrated that, unlike stable dendritic branches observed in pyramidal neurons, dendritic branches of inhibitory interneurons in the superficial layers of the cortex are very dynamic [57]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Lee WC 2006 Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex PLoS Biol 4 e29 16366735 PMC1318477 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Learning-induced spine formation occurs at the expense of spines that existed before learning, suggesting that homeostatic regulation could play an important role in maintaining stable spine density in the adult brain.

    “Furthermore, learning-induced spine formation occurs at the expense of spines that exist before learning [37], suggesting that homeostatic regulation could play an important role in maintaining stable spine density in the adult brain.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cajal-Retzius axons grow slowly along tortuous paths, while thalamocortical axons grow quickly and straight.

    “Cajal-Retzius axons grow slowly and follow tortuous paths, while thalamocortical axons grow quickly and straight [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Portera-Cailliau C 2005 Diverse modes of axon elaboration in the developing neocortex PLoS Biol 3 e272 16026180 PMC1180514 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    At this age, both axon types favor overall growth in the superficial cortical layers, with slightly more terminal extension than retraction.

    “At this age, both axon types favor an overall growth in the superficial cortical layers, with slightly more terminal extension than retraction [60].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Portera-Cailliau C 2005 Diverse modes of axon elaboration in the developing neocortex PLoS Biol 3 e272 16026180 PMC1180514 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    This interneuron synapse turnover is on the same order as dendritic spine turnover in L5 pyramidal neurons during sensory manipulation and motor learning, suggesting comparable degrees of structural remodeling of excitatory and inhibitory synapses in the adult cortex.

    “This is on the same order of dendritic spine turnover observed in L5 pyramidal neurons during sensory manipulation and motor learning [30, 37, 38], suggesting comparable degrees of structural remodeling of excitatory and inhibitory synapses in the adult cortex.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [30] Hofer SB 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 19005470 PMC6485433 source

      Not checked in the free run.

    • cites [37] Xu T 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 19946267 PMC2844762 source

      Not checked in the free run.

    • cites [38] Yang G 2009 Stably maintained dendritic spines are associated with lifelong memories Nature 462 920 924 19946265 PMC4724802 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The distribution of dynamic branches and the timeline of remodeling are laminar dependent.

    “The distribution of dynamic branches and the timeline of remodeling were also found to be laminar dependent [10].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Chen JL Nedivi E 2010 Neuronal structural remodeling: is it all about access? Curr Opin Neurobiol 20 557 562 20621466 PMC2946477 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Cortical axons undergo rapid and large-scale rearrangements during development and after injuries.

    “In summary, cortical axons undergo rapid and large-scale rearrangements both during development and in response to injuries.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Axons from mouse cortical L6 neurons contain a high density of small terminaux boutons, which are highly dynamic with about 60% turnover during the same period.

    “In contrast, axons from mouse cortical L6 neurons contain a high density of small terminaux boutons, which are highly dynamic with ~60% turnover during the same period [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] De Paola V 2006 Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex Neuron 49 861 875 16543134 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Thalamocortical axons contain large terminaux boutons and en passant boutons, which are mostly stable, with 85% of boutons persisting over a month.

    “Thalamocortical axons contain large terminaux boutons and en passant boutons, which are mostly stable with 85% boutons persisting over a month [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] De Paola V 2006 Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex Neuron 49 861 875 16543134 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Spine volume correlates with the size of the postsynaptic density and the number of presynaptic vesicles.

    “In the case of dendritic spines, evidence from classic electron microscopy (EM) studies has demonstrated that spine volume correlates with the size of the postsynaptic density and the number of presynaptic vesicles (see reviews [23, 64]), suggesting that larger spines have stronger synapses.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [23] Bourne JN Harris KM 2008 Balancing structure and function at hippocampal dendritic spines Annu Rev Neurosci 31 47 67 18284372 PMC2561948 source

      Not checked in the free run.

    • cites [64] Arellano JI 2007 Ultrastructure of dendritic spines: correlation between synaptic and spine morphologies Front Neurosci 1 131 143 18982124 PMC2518053 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    In adults, a small subset of synaptic structures turn over rapidly despite global stability of axons and dendrites.

    “In adults, despite the global stability of axonal and dendritic stability, a small subset of synaptic structures have been observed to turn over rapidly.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Recent developments in high-throughput, automated sectioning and imaging overcome the impasse and potentially make ultrastructural analysis of imaged tissues routine.

    “Recent developments in high-throughput, automated sectioning and imaging overcome this impasse and potentially make ultrastructural analysis of imaged tissues routine [86, 87].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [86] Knott GW 2009 A protocol for preparing GFP-labeled neurons previously imaged in vivo and in slice preparations for light and electron microscopic analysis Nat Protoc 4 1145 1156 19617886 source

      Not checked in the free run.

    • cites [87] Knott G 2008 Serial section scanning electron microscopy of adult brain tissue using focused ion beam milling J Neurosci 28 2959 2964 18353998 PMC6670719 source

      Not checked in the free run.

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

    Premisecitation

    Recent development of genetically encoded calcium indicators and innovations in imaging neuronal activity in awake, head-fixed mice have opened new opportunities toward studying structural-functional relationships.

    “The recent development of genetically encoded calcium indicators [89–91] and innovations in imaging neuronal activity in awake, head-fixed mice [92–96] have opened new opportunities toward this direction.”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [89] Tian L 2009 Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators Nat Methods 6 875 881 19898485 PMC2858873 source

      Not checked in the free run.

    • cites [90] Mank M 2008 A genetically encoded calcium indicator for chronic in vivo two-photon imaging Nat Methods 5 805 811 19160515 PMC7618336 source

      Not checked in the free run.

    • cites [91] Wallace DJ 2008 Single-spike detection in vitro and in vivo with a genetic Ca2+ sensor Nat Methods 5 797 804 19160514 source

      Not checked in the free run.

    • cites [92] Dombeck DA 2007 Imaging large-scale neural activity with cellular resolution in awake, mobile mice Neuron 56 43 57 17920014 PMC2268027 source

      Not checked in the free run.

    • cites [93] Andermann ML 2010 Chronic cellular imaging of mouse visual cortex during operant behavior and passive viewing Front Cell Neurosci 4 3 20407583 PMC2854571

      Not checked in the free run.

    • cites [94] Niell CM Stryker MP 2010 Modulation of visual responses by behavioral state in mouse visual cortex Neuron 65 472 479 20188652 PMC3184003 source

      Not checked in the free run.

    • cites [95] Komiyama T 2010 Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice Nature 464 1182 1186 20376005 source

      Not checked in the free run.

    • cites [96] Dombeck DA 2010 Functional imaging of hippocampal place cells at cellular resolution during virtual navigation Nat Neurosci 13 1433 1440 20890294 PMC2967725 source

      Not checked in the free run.

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

    Premisenone given

    Most cell-type-specific lines label the whole population of target cell types and are useful for molecular examination and manipulation, but imaging them is challenging due to high density of neurons and/or dim expression of the EGFP reporter gene.

    “While most cell-type-specific lines label the whole population of target cell types and are useful for molecular examination and manipulation, imaging them is challenging due to the high density of neurons within the cortex and/or dim expression of the EGFP reporter gene.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The Gene Expression Nervous System Atlas (GENSAT) project has generated hundreds of mouse lines that express EGFP under different bacterial artificial chromosomes (BACs).

    “The Gene Expression Nervous System Atlas (GENSAT) project has generated hundreds of mouse lines that express EGFP under different bacterial artificial chromosomes (BACs) [83, 84].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [83] Gong S 2003 A gene expression atlas of the central nervous system based on bacterial artificial chromosomes Nature 425 917 925 14586460 source

      Not checked in the free run.

    • cites [84] Heintz N 2004 Gene expression nervous system atlas (GENSAT) Nat Neurosci 7 483 15114362 source

      Not checked in the free run.

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

    Premisecitation

    A recent screen using GENSAT lines has identified several mouse lines selectively labeling inhibitory neurons in unique retinal circuits.

    “A recent screen using these lines has identified several mouse lines selectively labeling inhibitory neurons in unique retinal circuits [85].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Siegert S 2009 Genetic address book for retinal cell types Nat Neurosci 12 1197 1204 19648912 source

      Not checked in the free run.

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

    Premisecitation

    Functional imaging of individual hippocampal pyramidal neurons during spatial navigation in behaving mice has recently been described.

    “For instance, the functional imaging of individual hippocampal pyramidal neurons during spatial navigation in behaving mice has recently been described [96].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Dombeck DA 2010 Functional imaging of hippocampal place cells at cellular resolution during virtual navigation Nat Neurosci 13 1433 1440 20890294 PMC2967725 source

      Not checked in the free run.

52 of 52

  • The paper relies on this without support.

    Synapses are located along the dendrites of aspiny interneurons.

    “Given the fact that synapses are located along dendrites of aspiny interneurons”

  • The paper relies on this without support.

    In vivo structural imaging is currently limited to superficial cortical layers (mostly L1 and L2) due to limitations of current two-photon laser scanning systems.

    “Due to the limitation of current two-photon laser scanning systems, in vivo structural imaging is currently limited to superficial cortical layers (mostly L1 and L2).”

  • The paper relies on this without support.

    Different cortical layers have different connectivity.

    “Given the different connectivity between the different cortical layers, it may not be appropriate to simply extend the present understanding obtained from superficial layers to deeper layers of the cortex.”
3 of 3

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?

  • Experience-dependent mechanisms regulate the sensitivity and plasticity of the central nervous system and act at several biological levels: cellular changes such as neurogenesis, pruning and sprouting of synapses, myelination of axons and alterations to the number of dendritic spines; subcellular changes, such as alterations to the cytoskeleton and the extracellular matrix and changes in the level

    “These experience-dependent mechanisms regulate the sensitivity and plasticity of the central nervous system and act at several biological levels (likely partly in parallel with each other): i) cellular changes such as neurogenesis, pruning and sprouting of synapses, myelination of axons and alterations to the number of dendritic spines9, 10, ii) subcellular changes, such as alterations to the”

    From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [10]

  • Spine morphology and dynamics vary among neuronal types, across developmental stages, and in response to experiences such as sensory stimulation and deprivation, environmental enrichment, and various paradigms of learning.

    “Furthermore, their morphology and dynamics vary among neuronal types, across developmental stages, and in response to experiences such as sensory stimulation and deprivation, environmental enrichment, and various paradigms of learning (Holtmaat and Svoboda, 2009; Fu and Zuo, 2011).”

    From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Fu and Zuo, 2011

Cites

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Research works printed but not linked: 1

  1. James, 1890, Vol. 1

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Related

Authors
Fu, M., & Zuo, Y.
Affiliations
University of California, Santa Cruz (US)
Corresponding author
Zuo, Yi
ORCID
Zuo, Yi
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2011-04
Volume
34
Issue
4
Pages
177-187
ISSN
0166-2236 (ISSN-L)
DOI
10.1016/j.tins.2011.02.001
PMC
PMC3073830
OpenAlex
W2105232223
Cited by
322
References
97
Citations by year
2026: 21 · 2025: 16 · 2024: 15 · 2023: 17 · 2022: 18 · 2021: 29 · 2020: 18 · 2019: 17 · 2018: 21 · 2017: 24 · 2016: 13 · 2015: 26 · 2014: 25 · 2013: 32 · 2012: 23
FWCI
2.65
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Ellison Medical Foundation
  • National Institute on Aging (R01AG031871)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
experience-dependent plasticity, structural synaptic plasticity, cortical synapses, synaptic pruning, synaptogenesis, two-photon imaging, time-lapse imaging, sensorimotor learning, memory consolidation, cortical layers, neuronal cell types, circuit plasticity
MeSH terms
Animals, Cerebral Cortex, Dendrites, Learning, Memory, Neuronal Plasticity, Synapses, Time-Lapse Imaging

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