Chronic 2P-STED imaging reveals high turnover of dendritic spines in the hippocampus in vivo
Open accessAbstract
Rewiring neural circuits by the formation and elimination of synapses is thought to be a key cellular mechanism of learning and memory in the mammalian brain. Dendritic spines are the postsynaptic structural component of excitatory synapses, and their experience-dependent plasticity has been extensively studied in mouse superficial cortex using two-photon microscopy in vivo. By contrast, very little is known about spine plasticity in the hippocampus, which is the archetypical memory center of the brain, mostly because it is difficult to visualize dendritic spines in this deeply embedded structure with sufficient spatial resolution. We developed chronic 2P-STED microscopy in mouse hippocampus, using a ‘hippocampal window’ based on resection of cortical tissue and a long working distance objective for optical access. We observed a two-fold higher spine density than previous studies and measured a spine turnover of ~40% within 4 days, which depended on spine size. We thus provide direct evidence for a high level of structural rewiring of synaptic circuits and new insights into the structure-dynamics relationship of hippocampal spines. Having established chronic super-resolution microscopy in the hippocampus in vivo, our study enables longitudinal and correlative analyses of nanoscale neuroanatomical structures with genetic, molecular and behavioral experiments.
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.
Integrity signals
Registry
Cites
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.
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?
A substantial portion of dendritic spines on CA1 pyramidal cells turn over within a few weeks.
“Perhaps even more problematic is the report that a substantial portion of dendritic spines on CA1 pyramidal cells turn over within a few weeks (416, 417).”
From Synaptic memory and CaMKII (2023) · cites this paper as [417]
Non-super-resolution light microscopy-based methods fail to resolve short-necked spines and are more likely to fail to detect spines in the z-direction.
“Non-super-resolution light microscopy-based methods fail to resolve short-necked spines and are more likely to fail to detect spines in the z-direction (Pfeiffer et al., 2018; Tønnesen et al., 2014).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Pfeiffer et al., 2018
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 53 · Cited by 192
Research works printed but not linked: 42
- Berning S Willig KI Steffens H Dibaj P Hell SW 2012 Nanoscopy in a living mouse brain Science 335 551 10.1126/science.1215369 22301313 · DOI · Paper page
- Bloss EB Cembrowski MS Karsh B Colonell J Fetter RD Spruston N 2018 Single excitatory axons form clustered synapses onto CA1 pyramidal cell dendrites Nature Neuroscience 21 353 363 10.1038/s41593-018-0084-6 29459763 · DOI
- Brigman JL Wright T Talani G Prasad-Mulcare S Jinde S Seabold GK Mathur P Davis MI Bock R Gustin RM Colbran RJ Alvarez VA Nakazawa K Delpire E Lovinger DM Holmes A 2010 Loss of GluN2B-containing NMDA receptors in CA1 hippocampus and cortex impairs long-term depression, reduces dendritic spine density, and disrupts learning Journal of Neuroscience 30 4590 4600 10.1523/JNEUROSCI.0640-10.2010 20357110 PMC2869199 · DOI · Paper page
- Cappaert NLM Van Strien NM Witter MP 2014 Paxinos G The Rat Nervous System fourth ed Burlington Elsevier Science 1053
- Dombeck DA Harvey CD Tian L Looger LL Tank DW 2010 Functional imaging of hippocampal place cells at cellular resolution during virtual navigation Nature Neuroscience 13 1433 1440 10.1038/nn.2648 20890294 PMC2967725 · DOI · Paper page
- Engert F Bonhoeffer T 1999 Dendritic spine changes associated with hippocampal long-term synaptic plasticity Nature 399 66 70 10.1038/19978 10331391 · DOI
- Feng G Mellor RH Bernstein M Keller-Peck C Nguyen QT Wallace M Nerbonne JM Lichtman JW Sanes JR 2000 Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP Neuron 28 41 51 10.1016/S0896-6273(00)00084-2 11086982 · DOI · Paper page
- Frankland PW Bontempi B 2005 The organization of recent and remote memories Nature Reviews Neuroscience 6 119 130 10.1038/nrn1607 15685217 · DOI · Paper page
- Fuhrmann M Mitteregger G Kretzschmar H Herms J 2007 Dendritic pathology in prion disease starts at the synaptic spine Journal of Neuroscience 27 6224 6233 10.1523/JNEUROSCI.5062-06.2007 17553995 PMC6672160 · DOI
- Gould TJ Burke D Bewersdorf J Booth MJ 2012 Adaptive optics enables 3D STED microscopy in aberrating specimens Optics Express 20 20998 21009 10.1364/OE.20.020998 23037223 PMC3635694 · DOI
- Gu L Kleiber S Schmid L Nebeling F Chamoun M Steffen J Wagner J Fuhrmann M 2014 Long-term in vivo imaging of dendritic spines in the hippocampus reveals structural plasticity Journal of Neuroscience 34 13948 13953 10.1523/JNEUROSCI.1464-14.2014 25319691 PMC6705298 · DOI
- Harris KM Jensen FE Tsao B 1992 Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation Journal of Neuroscience 12 2685 2705 1613552 PMC6575840
- Hayashi-Takagi A Yagishita S Nakamura M Shirai F Wu YI Loshbaugh AL Kuhlman B Hahn KM Kasai H 2015 Labelling and optical erasure of synaptic memory traces in the motor cortex Nature 525 333 338 10.1038/nature15257 26352471 PMC4634641 · DOI · Paper page
- Hell SW 2007 Far-field optical nanoscopy Science 316 1153 1158 10.1126/science.1137395 17525330 · DOI · Paper page
- Hofer SB Mrsic-Flogel TD Bonhoeffer T Hübener M 2009 Experience leaves a lasting structural trace in cortical circuits Nature 457 313 317 10.1038/nature07487 19005470 PMC6485433 · DOI · Paper page
- Holtmaat A Wilbrecht L Knott GW Welker E Svoboda K 2006 Experience-dependent and cell-type-specific spine growth in the neocortex Nature 441 979 983 10.1038/nature04783 16791195 · DOI · Paper page
- Holtmaat AJ Trachtenberg JT Wilbrecht L Shepherd GM Zhang X Knott GW Svoboda K 2005 Transient and persistent dendritic spines in the neocortex in vivo Neuron 45 279 291 10.1016/j.neuron.2005.01.003 15664179 · DOI · Paper page
- Ji N 2017 Adaptive optical fluorescence microscopy Nature Methods 14 374 380 10.1038/nmeth.4218 28362438 · DOI
- Kasai H Fukuda M Watanabe S Hayashi-Takagi A Noguchi J 2010 Structural dynamics of dendritic spines in memory and cognition Trends in Neurosciences 33 121 129 10.1016/j.tins.2010.01.001 20138375 · DOI · Paper page
- Keck T Mrsic-Flogel TD Vaz Afonso M Eysel UT Bonhoeffer T Hübener M 2008 Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex Nature Neuroscience 11 1162 1167 10.1038/nn.2181 18758460 · DOI · Paper page
- Keck T Scheuss V Jacobsen RI Wierenga CJ Eysel UT Bonhoeffer T Hübener M 2011 Loss of sensory input causes rapid structural changes of inhibitory neurons in adult mouse visual cortex Neuron 71 869 882 10.1016/j.neuron.2011.06.034 21903080 · DOI
- Klar TA Jakobs S Dyba M Egner A Hell SW 2000 Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission PNAS 97 8206 8210 10.1073/pnas.97.15.8206 10899992 PMC26924 · DOI · Paper page
- Knott GW Holtmaat A Wilbrecht L Welker E Svoboda K 2006 Spine growth precedes synapse formation in the adult neocortex in vivo Nature Neuroscience 9 1117 1124 10.1038/nn1747 16892056 · DOI · Paper page
- Lue N Bewersdorf J Lessard MD Badizadegan K Dasari RR Feld MS Popescu G 2007 Tissue refractometry using Hilbert phase microscopy Optics Letters 32 3522 3524 10.1364/OL.32.003522 18087529 PMC2677691 · DOI
- Majewska AK Newton JR Sur M 2006 Remodeling of synaptic structure in sensory cortical areas in vivo Journal of Neuroscience 26 3021 3029 10.1523/JNEUROSCI.4454-05.2006 16540580 PMC6673961 · DOI
- Marinković S Milisavljević M Puskas L 1992 Microvascular anatomy of the hippocampal formation Surgical Neurology 37 339 349 10.1016/0090-3019(92)90001-4 1631758 · DOI
- Mizrahi A Crowley JC Shtoyerman E Katz LC 2004 High-resolution in vivo imaging of hippocampal dendrites and spines Journal of Neuroscience 24 3147 3151 10.1523/JNEUROSCI.5218-03.2004 15056694 PMC6730023 · DOI
- Nägerl UV Eberhorn N Cambridge SB Bonhoeffer T 2004 Bidirectional activity-dependent morphological plasticity in hippocampal neurons Neuron 44 759 767 10.1016/j.neuron.2004.11.016 15572108 · DOI · Paper page
- Nimchinsky EA Sabatini BL Svoboda K 2002 Structure and function of dendritic spines Annual Review of Physiology 64 313 353 10.1146/annurev.physiol.64.081501.160008 11826272 · DOI · Paper page
- Noguchi J Nagaoka A Watanabe S Ellis-Davies GC Kitamura K Kano M Matsuzaki M Kasai H 2011 In vivo two-photon uncaging of glutamate revealing the structure-function relationships of dendritic spines in the neocortex of adult mice The Journal of Physiology 589 2447 2457 10.1113/jphysiol.2011.207100 21486811 PMC3115818 · DOI
- Patton BR Burke D Owald D Gould TJ Bewersdorf J Booth MJ 2016 Three-dimensional STED microscopy of aberrating tissue using dual adaptive optics Optics Express 24 8862 8876 10.1364/OE.24.008862 27137319 · DOI
- Sala C Segal M 2014 Dendritic spines: the locus of structural and functional plasticity Physiological Reviews 94 141 188 10.1152/physrev.00012.2013 24382885 · DOI
- Schmid LC Mittag M Poll S Steffen J Wagner J Geis HR Schwarz I Schmidt B Schwarz MK Remy S Fuhrmann M 2016 Dysfunction of somatostatin-positive interneurons associated with memory deficits in an alzheimer's disease model Neuron 92 114 125 10.1016/j.neuron.2016.08.034 27641495 · DOI
- Somogyi P 2010 Hippocampus – Intrinsic Organisation New York Oxford University Press
- Tønnesen J Katona G Rózsa B Nägerl UV 2014 Spine neck plasticity regulates compartmentalization of synapses Nature Neuroscience 17 678 685 10.1038/nn.3682 24657968 · DOI · Paper page
- Ter Veer MJT Pfeiffer T Nägerl UV 2017 Two-Photon STED microscopy for nanoscale imaging of neural morphology in vivo Methods in Molecular Biology 1663 45 64 10.1007/978-1-4939-7265-4_5 28924658 · DOI
- 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
- Urban NT Willig KI Hell SW Nägerl UV 2011 STED nanoscopy of actin dynamics in synapses deep inside living brain slices Biophysical Journal 101 1277 1284 10.1016/j.bpj.2011.07.027 21889466 PMC3164186 · DOI
- Willig KI Steffens H Gregor C Herholt A Rossner MJ Hell SW 2014 Nanoscopy of filamentous actin in cortical dendrites of a living mouse Biophysical Journal 106 L01 L03 10.1016/j.bpj.2013.11.1119 24411266 PMC3907229 · DOI
- Xu T Yu X Perlik AJ Tobin WF Zweig JA Tennant K Jones T Zuo Y 2009 Rapid formation and selective stabilization of synapses for enduring motor memories Nature 462 915 919 10.1038/nature08389 19946267 PMC2844762 · DOI · Paper page
- 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
- Yuste R Bonhoeffer T 2004 Genesis of dendritic spines: insights from ultrastructural and imaging studies Nature Reviews Neuroscience 5 24 34 10.1038/nrn1300 14708001 · DOI
- Authors
- Pfeiffer, T., Poll, S., Bancelin, S., Angibaud, J., Inavalli, V. K., Keppler, K., Mittag, M., Fuhrmann, M., & Nägerl, U. V.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- German Center for Neurodegenerative Diseases (DE)
- Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France
- Corresponding author
- Fuhrmann, Martin
- Nägerl, U Valentin
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-06-22
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6014725
- OpenAlex
- W2809205951
- Cited by
- 192
- References
- 53
- Citations by year
- 2026: 18 · 2025: 21 · 2024: 22 · 2023: 26 · 2022: 18 · 2021: 37 · 2020: 25 · 2019: 24 · 2018: 1
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- ePrints Soton (University of Southampton) (submittedVersion)
- DZNE Pub (submittedVersion, cc-by)
- Funders
- Fondation pour la Recherche Médicale (DEQ20160334901, Graduate Student Fellowship 634FDT20160435677)
- COEN (ANR-16-COEN-0003-02, CoEN3018)
- Deutsche Forschungsgemeinschaft (SFB1089)
- ERA-Net (MicroSynDep)
- Boehringer Ingelheim Fonds (Graduate Student Fellowship)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- dendritic spines, hippocampus, STED microscopy, super-resolution imaging, synaptic plasticity, excitatory synapses, spine density, learning and memory, in vivo imaging
- MeSH terms
- Animals, Bacterial Proteins, Cerebral Cortex, Female, Hippocampus, Image Processing, Computer-Assisted, Luminescent Proteins, Male, Memory, Mice, Transgenic, Nerve Net, Neuronal Plasticity, Synapses, Gene Expression, Genes, Reporter, Pyramidal Cells, Microscopy, Fluorescence, Multiphoton, Dendritic Spines, Green Fluorescent Proteins, Mice, Molecular Imaging
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