Synaptic plasticity and super-resolution microscopy
The biology of synapses is an extremely productive and interdisciplinary scientific endeavor, harboring central questions of cell biology and neuroscience. Synapses are physical sites of intercellular contact that transmit and transform information in a very rapid and flexible way, playing a pivotal role for learning and memory formation as well as neurological diseases of the mammalian brain.
Since synapses are tiny and densely packed in light-scattering brain tissue, understanding their dynamic behavior in mechanistic terms under physiological conditions is a serious experimental challenge. Fortunately, recent technological innovations, particularly in labeling and live-cell imaging techniques, are helping to break new ground. The advent of fluorescence microscopy beyond the diffraction limit has opened up huge experimental opportunities to directly image and resolve key physiological signaling events inside single synapses in intact brain tissue, a possibility which was considered a pipedream until recently.
Our group is invested in harnessing these exciting technological developments to study synapses in their natural habitat and under realistic conditions, aiming to better understand higher brain function and disorders in terms of the underlying synaptic mechanisms.
To this end, we are applying novel super-resolution microscopy approaches (STED microscopy), giving us a much more complete and refined view of the dynamic behavior and plasticity of neuronal synapses and their interactions with glia cells inside living brain slices and in the intact mouse brain in vivo. These approaches are complemented by a combination of 2-photon imaging & photoactivation and patch-clamp electrophysiology aided by tools from molecular genetics.
Mots clés
AVC, Adhésion cellulaire et cytosquelette, Alzheimer, Analyses des données, Apprentissage, Bio-senseurs, Codage et intégration du signal, Connectivité, Excitabilité neuronale, Interactions neurones-glie, Microscopie super-résolutive, Mémoire, Neurophysiologie, Physiologie synaptique, Plasticité synaptique, Ultrastructure neuronale et morphogénèseSelected publications
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Impact of a tilted coverslip on two-photon and STED microscopy
Guillaume Le Bourdellès, Luc Mercier, Johannes Roos, Stéphane Bancelin, U. Valentin Nägerl.
Biomed. Opt. Express. 2024-01-16. 15 (2) : 743.
DOI: 10.1364/BOE.510512 -
Shadow imaging for panoptical visualization of brain tissue in vivo
Yulia Dembitskaya, Andrew K. J. Boyce, Agata Idziak, Atefeh Pourkhalili Langeroudi, Misa Arizono, Jordan Girard, Guillaume Le Bourdellès, Mathieu Ducros, Marie Sato-Fitoussi, Amaia Ochoa de Amezaga, Kristell Oizel, Stephane Bancelin, Luc Mercier, Thomas Pfeiffer, Roger J. Thompson, Sun Kwang Kim, Andreas Bikfalvi, U. Valentin Nägerl.
Nat Commun. 2023-10-12. 14 (1)
DOI: 10.1038/s41467-023-42055-2 -
Il faut être trois pour danser le tango
Misa Arizono, Agata Idziak, U. Valentin Nägerl.
Med Sci (Paris). 2021-02-01. 37 (2) : 127-129.
DOI: 10.1051/medsci/2020275 -
Aberration correction in STED microscopy to increase imaging depth in living brain tissue
Stéphane Bancelin, Luc Mercier, Emanuele Murana, Valentin Nägerl.
Preprint bioRxiv. 2021-01-06.
DOI: 10.1101/2021.01.05.425408 -
Super-resolution shadow imaging reveals local remodeling of astrocytic microstructures and brain extracellular space after osmotic challenge
Misa Arizono, Krishna VVG Inavalli, Valentin Nagerl.
Preprint bioRxiv. 2021-01-05.
DOI: 10.1101/2021.01.05.425369 -
Turning up the Green Light
Julien Cassereau, Vincent Courdavault, U. Valentin Nägerl.
Trends in Cell Biology. 2020-12-01.
DOI: 10.1016/j.tcb.2020.12.007 -
Ultrastructural Imaging of Activity-Dependent Synaptic Membrane-Trafficking Events in Cultured Brain Slices
Cordelia Imig, Francisco José López-Murcia, Lydia Mau,s Inés Hojas García-Plaza, Lena Sünke Mortensen, Manuela Schwark, Valentin Schwarze, Julie Angibaud, U. Valentin Nägerl, Holger Taschenberger, Nils Brose, Benjamin H. Cooper.
Neuron. 2020-09-28. 108 : 1-18.
DOI: 10.1016/j.neuron.2020.09.004 -
Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance
Bettina Stolp, Flavian Thelen, Xenia Ficht, Lukas M. Altenburger, Nora Ruef, V. V. G. Krishna Inavalli, Philipp Germann, Nicolas Page, Federica Moalli, Andrea Raimondi, Kirsten A. Keyser, S. Morteza Seyed Jafari, Francesca Barone, Matthias S. Dettmer, Doron Merkler, Matteo Iannacone, James Sharpe, Christoph Schlapbach, Oliver T. Fackler, U. Valentin Nägerl, Jens V. Stein.
Sci. Immunol.. 2020-04-03. 5 (46) : eaaz4371.
DOI: 10.1126/sciimmunol.aaz4371 -
SpineJ: A software tool for quantitative analysis of nanoscale spine morphology
Florian Levet, Jan Tønnesen, U. Valentin Nägerl, Jean-Baptiste Sibarita.
Methods. 2020-03-01. 174 : 49-55.
DOI: 10.1016/j.ymeth.2020.01.020 -
A super-resolution platform for correlative live single-molecule imaging and STED microscopy
V. V. G. Krishna Inavalli, Martin O. Lenz, Corey Butler, Julie Angibaud, Benjamin Compans, Florian Levet, Jan Tønnesen, Olivier Rossier, Gregory Giannone, Olivier Thoumine, Eric Hosy, Daniel Choquet, Jean-Baptiste Sibarita, U. Valentin Nägerl.
Nat Methods. 2019-10-21.
DOI: 10.1038/s41592-019-0611-8 -
SpineJ : A software tool for quantitative analysis of nanoscale spine morphology
Florian Levet, Jan Tønnesen, Valentin Nägerl, Jean-Baptiste Sibarita.
. 2019-09-10.
DOI: 10.1101/764548 -
Simulation of calcium signaling in fine astrocytic processes: Effect of spatial properties on spontaneous activity
Audrey DENIZOT, Misa ARIZONO, U. Valentin NÄGERL, Hédi SOULA, Hugues BERRY.
PLoS Comput Biol. 2019-08-19. 15 (8) : e1006795.
DOI: 10.1371/journal.pcbi.1006795 -
Unveiling the Extracellular Space of the Brain: From Super-resolved Microstructure to In Vivo Function
Sabina Hrabetova, Laurent Cognet, Dmitri A. Rusakov, U. Valentin Nägerl.
J. Neurosci.. 2018-10-31. 38 (44) : 9355-9363.
DOI: 10.1523/JNEUROSCI.1664-18.2018 -
Chronic 2P-STED imaging reveals high turnover of dendritic spines in the hippocampus in vivo
Thomas Pfeiffer, Stefanie Poll, Stephane Bancelin, Julie Angibaud, VVG Krishna Inavalli, Kevin Keppler, Manuel Mittag, Martin Fuhrmann, U Valentin Nägerl.
eLife. 2018-06-22. 7
DOI: 10.7554/eLife.34700 -
Astroglia withdraw from potentiated synapses boosting inter-synaptic cross-talk
Christian Henneberger, Lucie Bard, Aude Panatier, James P. Reynolds, Nikolay I. Medvidov, Daniel Minge, Michel K. Herde, Stefanie Anders, Igor Kraev, Kaiyu Zheng, Thomas P. Jensen, Inmaculada Sanchez-Romero, Harald Janovjak, Ole-Petter Ottersen, Erlend-Arnulf Nagelhus, Stéphane H.R. Oliet, Michael G. Stewart, U. Valentin Nagerl, Dmitri A. Rusakov.
. 2018-06-17.
DOI: 10.1101/349233 -
Evidence for altered dendritic spine compartmentalization in Alzheimer’s disease and functional effects in a mouse model
Alexandre Androuin, Brigitte Potier, U. Valentin Nägerl, Daniel Cattaert, Lydia Danglot, Manon Thierry, Ihsen Youssef, Antoine Triller, Charles Duyckaerts, Khalid Hamid El Hachimi, Patrick Dutar, Benoît Delatour, Serge Marty.
Acta Neuropathol. 2018-04-25. 135 (6) : 839-854.
DOI: 10.1007/s00401-018-1847-6 -
Super-Resolution Imaging of the Extracellular Space in Living Brain Tissue
Jan Tønnesen, V.V.G. Krishna Inavalli, U. Valentin Nägerl.
Cell. 2018-02-01. 172 (5) : 1108-1121.e15.
DOI: 10.1016/j.cell.2018.02.007 -
APC/CCdh1-Rock2 pathway controls dendritic integrity and memory
Verónica Bobo-Jiménez, María Delgado-Esteban, Julie Angibaud, Irene Sánchez-Morán, Antonio de la Fuente, Javier Yajeya, U. Valentin Nägerl, José Castillo, Juan P. Bolaños, Angeles Almeida.
Proc Natl Acad Sci USA. 2017-04-10. 114 (17) : 4513-4518.
DOI: 10.1073/pnas.1616024114 -
Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity
Ronan Chéreau, G. Ezequiel Saraceno, Julie Angibaud, Daniel Cattaert, U. Valentin Nägerl.
Proc Natl Acad Sci USA. 2017-01-23. 114 (6) : 1401-1406.
DOI: 10.1073/pnas.1607541114 -
Two-Photon STED Microscopy for Nanoscale Imaging of Neural Morphology In Vivo
Mirelle J. T. ter Veer, Thomas Pfeiffer, U. Valentin Nägerl.
Methods in Molecular Biology. 2017-01-01. : 45-64.
DOI: 10.1007/978-1-4939-7265-4_5 -
Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines
Thomas Pfeiffer, Elena Avignone, U. Valentin Nägerl.
Sci Rep. 2016-09-08. 6 (1)
DOI: 10.1038/srep32422 -
Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors.
Silvia Viana da Silva, Matthias Georg Haberl, Pei Zhang, Philipp Bethge, Cristina Lemos, Nélio Gonçalves, Adam Gorlewicz, Meryl Malezieux, Francisco Q. Gonçalves, Noëlle Grosjean, Christophe Blanchet, Andreas Frick, U Valentin Nägerl, Rodrigo A. Cunha, Christophe Mulle.
Nat Comms. 2016-06-17. 7 : 11915.
DOI: 10.1038/ncomms11915 -
Dendritic Spines as Tunable Regulators of Synaptic Signals
Jan Tønnesen, U. Valentin Nägerl.
Front. Psychiatry. 2016-06-09. 7
DOI: 10.3389/fpsyt.2016.00101 -
Spines slow down dendritic chloride diffusion and affect short-term ionic plasticity of GABAergic inhibition.
Namrata Mohapatra, Jan Tønnesen, Andreas Vlachos, Thomas Kuner, Thomas Deller, U. Valentin Nägerl, Fidel Santamaria, Peter Jedlicka.
Sci Rep. 2016-03-18. 6 (1)
DOI: 10.1038/srep23196 -
Biochemical compartmentalization in dendrites
Fritjof Helmchen, U. Valentin Nägerl.
Dendrites. 2016-03-01. : 285-324.
DOI: 10.1093/acprof:oso/9780198745273.003.0010 -
Convergence of Hippocampal Pathophysiology in Syngap+/- and Fmr1-/y Mice.
S. A. Barnes, L. S. Wijetunge, A. D. Jackson, D. Katsanevaki, E. K. Osterweil, N. H. Komiyama, S. G. N. Grant, M. F. Bear, U. V. Nagerl, P. C. Kind, D. J. A. Wyllie.
Journal of Neuroscience. 2015-11-11. 35 (45) : 15073-15081.
DOI: 10.1523/JNEUROSCI.1087-15.2015 -
Altered morphological dynamics of activated microglia after induction of status epilepticus.
Elena Avignone, Marilyn Lepleux, Julie Angibaud, U. Valentin Nägerl.
J Neuroinflammation. 2015-11-04. 12 (1)
DOI: 10.1186/s12974-015-0421-6 -
STED microscopy for nanoscale imaging in living brain slices.
Ronan Chéreau, Jan Tønnesen, U. Valentin Nägerl.
Methods. 2015-10-01. 88 : 57-66.
DOI: 10.1016/j.ymeth.2015.06.006 -
Dissecting tripartite synapses with STED microscopy
A. Panatier, M. Arizono, U. V. Nagerl.
Philosophical Transactions of the Royal Society B: Biological Sciences. 2014-09-15. 369 (1654) : 20130597-20130597.
DOI: 10.1098/rstb.2013.0597 -
Stimulated emission depletion (STED) microscopy reveals nanoscale defects in the developmental trajectory of dendritic spine morphogenesis in a mouse model of fragile X syndrome.
L. S. Wijetunge, J. Angibaud, A. Frick, P. C. Kind, U. V. Nagerl.
Journal of Neuroscience. 2014-04-30. 34 (18) : 6405-6412.
DOI: 10.1523/JNEUROSCI.5302-13.2014 -
Spine neck plasticity regulates compartmentalization of synapses
Jan Tønnesen, Gergely Katona, Balázs Rózsa, U Valentin Nägerl.
Nat Neurosci. 2014-03-23. 17 (5) : 678-685.
DOI: 10.1038/nn.3682 -
Nanoscale Imaging of Synapses
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Neuromethods. 2014-01-01.
DOI: 10.1007/978-1-4614-9179-8 -
Two-Photon Excitation STED Microscopy for Imaging Synapses and Glia in Acute Brain Slices
Philipp Bethge, U. Valentin Nägerl.
Neuromethods. 2014-01-01. : 205-220.
DOI: 10.1007/978-1-4614-9179-8_11 -
Superresolution imaging for neuroscience
Jan Tønnesen, U. Valentin Nägerl.
Experimental Neurology. 2013-04-01. 242 : 33-40.
DOI: 10.1016/j.expneurol.2012.10.004 -
Two-photon excitation STED microscopy in two colors in acute brain slices.
Philipp Bethge, Ronan Chéreau, Elena Avignone, Giovanni Marsicano, U. Valentin Nägerl.
Biophysical Journal. 2013-02-01. 104 (4) : 778-785.
DOI: 10.1016/j.bpj.2012.12.054 -
3SBA-04 STED imaging of synapses in living brain slices : from structure to function(3SBA Cutting-edge optical imaging approach to neuroscience-From single molecule to in vivo-,Symposium)
U. Valentin Nagerl.
Biophysics. 2013-01-01. 53 (supplement1-2) : S102.
DOI: 10.2142/biophys.53.s102_2 -
Two-Color STED Imaging of Synapses in Living Brain Slices
Jan Tønnesen, U. Valentin Nägerl.
Nanoimaging. 2012-09-18. : 65-80.
DOI: 10.1007/978-1-62703-137-0_5 -
Stimulated Emission Depletion (STED) Imaging of Dendritic Spines in Living Hippocampal Slices
Katrin I. Willig, U. Valentin Nägerl.
Cold Spring Harb Protoc. 2012-05-01. 2012 (5) : pdb.prot069260.
DOI: 10.1101/pdb.prot069260 -
Beyond Abbe’s Resolution Barrier
U.Valentin Nägerl.
Cellular Imaging Techniques for Neuroscience and Beyond. 2012-01-01. : 35-54.
DOI: 10.1016/b978-0-12-385872-6.00002-7 -
Two-Color STED Microscopy of Living Synapses Using A Single Laser-Beam Pair
Jan Tønnesen, Fabien Nadrigny, Katrin I. Willig, Roland Wedlich-Söldner, U. Valentin Nägerl.
Biophysical Journal. 2011-11-01. 101 (10) : 2545-2552.
DOI: 10.1016/j.bpj.2011.10.011 -
In vivo imaging of intersynaptic vesicle exchange using VGLUT1 Venus knock-in mice.
E. Herzog, F. Nadrigny, K. Silm, C. Biesemann, I. Helling, T. Bersot, H. Steffens, R. Schwartzmann, U. V. Nagerl, S. El Mestikawy, J. Rhee, F. Kirchhoff, N. Brose.
Journal of Neuroscience. 2011-10-26. 31 (43) : 15544-15559.
DOI: 10.1523/JNEUROSCI.2073-11.2011 -
STED Nanoscopy of Actin Dynamics in Synapses Deep Inside Living Brain Slices
Nicolai T. Urban, Katrin I. Willig, Stefan W. Hell, U. Valentin Nägerl.
Biophysical Journal. 2011-09-01. 101 (5) : 1277-1284.
DOI: 10.1016/j.bpj.2011.07.027 -
A Global Spatial Similarity Optimization Scheme to Track Large Numbers of Dendritic Spines in Time-Lapse Confocal Microscopy
Qing Li, Zhigang Deng, Yong Zhang, Xiaobo Zhou, U. Valentin Nagerl, Stephen T. C. Wong.
IEEE Trans. Med. Imaging. 2011-03-01. 30 (3) : 632-641.
DOI: 10.1109/tmi.2010.2090354 -
Knowledge-Based Morphology Quantification of STED Dendritic Spine Images
Donggang Yu, T. D. Pham, Valentin Nägerl.
IFMBE Proceedings. 2011-01-01. : 1210-1213.
DOI: 10.1007/978-3-642-23508-5_313 -
Imaging living synapses at the nanoscale by STED microscopy.
U. V. Nagerl, T. Bonhoeffer.
Journal of Neuroscience. 2010-07-14. 30 (28) : 9341-9346.
DOI: 10.1523/JNEUROSCI.0990-10.2010 -
STED Nanoscopy in Living Cells using Live Cell Compatible Markers
Katrin I. Willig, Birka Hein, U. Valentin Nägerl, Stefan W. Hell.
Biophysical Journal. 2009-02-01. 96 (3) : 17a.
DOI: 10.1016/j.bpj.2008.12.988 -
Nanoscale imaging of living synapses by STED microscopy
Valentin Nägerl.
Neuroscience Research. 2009-01-01. 65 : S26.
DOI: 10.1016/j.neures.2009.09.1637 -
Live-cell imaging of dendritic spines by STED microscopy.
U. V. Nagerl, K. I. Willig, B. Hein, S. W. Hell, T. Bonhoeffer.
Proceedings of the National Academy of Sciences. 2008-11-21. 105 (48) : 18982-18987.
DOI: 10.1073/pnas.0810028105 -
LTD Induction Causes Morphological Changes of Presynaptic Boutons and Reduces Their Contacts with Spines
Nadine Becker, Corette J. Wierenga, Rosalina Fonseca, Tobias Bonhoeffer, U. Valentin Nägerl.
Neuron. 2008-11-01. 60 (4) : 590-597.
DOI: 10.1016/j.neuron.2008.09.018 -
Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons
U. V. Nagerl, G. Kostinger, J. C. Anderson, K. A. C. Martin, T. Bonhoeffer.
Journal of Neuroscience. 2007-07-25. 27 (30) : 8149-8156.
DOI: 10.1523/JNEUROSCI.0511-07.2007 -
A Balance of Protein Synthesis and Proteasome-Dependent Degradation Determines the Maintenance of LTP
Rosalina Fonseca, Ramunas M. Vabulas, F. Ulrich Hartl, Tobias Bonhoeffer, U. Valentin Nägerl.
Neuron. 2006-10-01. 52 (2) : 239-245.
DOI: 10.1016/j.neuron.2006.08.015 -
Neuronal activity determines the protein synthesis dependence of long-term potentiation
Rosalina Fonseca, U Valentin Nägerl, Tobias Bonhoeffer.
Nat Neurosci. 2006-03-12. 9 (4) : 478-480.
DOI: 10.1038/nn1667 -
Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion.
Naoto Kawakami, U. Valentin Nägerl, Francesca Odoardi, Tobias Bonhoeffer, Hartmut Wekerle, Alexander Flügel.
J Exp Med. 2005-06-06. 201 (11) : 1805-1814.
DOI: 10.1084/jem.20050011 -
Competing for memory: hippocampal LTP under regimes of reduced protein synthesis.
Rosalina Fonseca, U.Valentin Nägerl, Richard G.M. Morris, Tobias Bonhoeffer.
Neuron. 2004-12-01. 44 (6) : 1011-1020.
DOI: 10.1016/j.neuron.2004.10.033 -
Bidirectional Activity-Dependent Morphological Plasticity in Hippocampal Neurons
U.Valentin Nägerl, Nicola Eberhorn, Sidney B. Cambridge, Tobias Bonhoeffer.
Neuron. 2004-12-01. 44 (5) : 759-767.
DOI: 10.1016/j.neuron.2004.11.016 -
Spatial micromovements of uncemented femoral components after torsional loads.
U. V. Nägerl.
J Biomech Eng. 2002-12-27. 124 (6) : 706.
DOI: 10.1115/1.1517565 -
Binding Kinetics of Calbindin-D28k Determined by Flash Photolysis of Caged Ca2+
U. Valentin Nägerl, David Novo, Istvan Mody, Julio L. Vergara.
Biophysical Journal. 2000-12-01. 79 (6) : 3009-3018.
DOI: 10.1016/s0006-3495(00)76537-4 -
Bending vibrations of the femur and the oscillatory behavior of a cemented femoral hip endoprosthesis.
A. Görtz.
J Biomech Eng. 2000-02-28. 122 (4) : 416.
DOI: 10.1115/1.1286317 -
Calcium-dependent inactivation of high-threshold calcium currents in human dentate gyrus granule cells
U. Valentin Nägerl, Istvan Mody.
The Journal of Physiology. 1998-05-01. 509 (1) : 39-45.
DOI: 10.1111/j.1469-7793.1998.039bo.x
Team member(s)
Chercheurs, Praticiens hospitaliers...
Ingénieur(e)s, technicien(ne)s
Post-doctorant(s)
Doctorant(s)
Neuropsychologist(s) and speech therapist(s)
Ingénieur(s) hospitalier(s) et ARC