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Synaptic Plasticity and Super-Resolution Microscopy

Team Leader : Valentin Nägerl

Bienvenue! Welcome! Willkommen! Yōkoso! Powitanie! Benvenuti! Dobro pozhalovat!

I am a full Professor of Neuroscience and Bioimaging and lead the research group 'Synaptic Plasticity and Super-Resolution Microcopy' at the Interdisciplinary Institute for NeuroScience. I also help run the Graduate School for Light Science and Technologies (EUR Light S&T) at the University of Bordeaux.

After undergrad studies in physics and medicine at the University of Göttingen, I got my PhD in neuroscience from UCLA with Istvan Mody and did a postdoc at the Max Planck Institute of Neurobiology with Tobias Bonhoeffer, spending research visits at the Max Planck Institute for Biophysical Chemistry with the Nobel laureate-to-be Stefan Hell. In 2009, I obtained the habilitation for neuroscience from the Technical University of Munich with Arthur Konnerth, before setting up my own laboratory in Bordeaux. In 2017, I became a senior member of the 'Institut Universitaire de France' (IUF), and our work has been recognized by an 'Equipe FRM' award (2016) and a Research Prize from the French Academy of Sciences (2018). In addition, I have received two highly competitive HFSP program awards (in 2010 and 2020).

My team is working at the interface of optical method development and neuroscience research, animated by the siren call of powerful new technology, academic freedom and the joy of tackling challenging projects together with amazing collaborators here in Bordeaux and across the globe. The team is relatively small, but we have a good fighting spirit and excellent working conditions at Bordeaux NeurocampusDriven by curiosity and instinct, we seek to decipher the enigmatic wonders of the brain and to help get the next generation of neuroscientists excited and ready for this mission.

Over the next few years, our research will be funded by the Human Frontier Science Program (HFSP) and European Research Council (ERC), giving me a fantastic chance to realize some of my wilder scientific dreams.

General objective

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 pipe dream until recently. My 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 developing and applying powerful 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. Recently, we invented super-resolution shadow imaging (SUSHI), a new technique to visualize the extracellular space of the brain (ECS), which is an important, however understudied, brain compartment for neural signaling and brain homeostasis. These core approaches are complemented by a combination of 2-photon imaging & photoactivation, patch-clamp electrophysiology and mathematical modeling aided by tools from molecular genetics and computational image analysis.

Check out our papers on PubMed, BioRXivOrcid, Google scholar.

Research Projects

Contribution of IP3 receptors and endoplasmic reticulum to calcium signalling in astrocytes

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Role of astrocyte aquaporin-4 in brain structure remodeling after traumatic brain injury: a combined MRI and STED microscopy study

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Multi-scale investigation of synaptic dysfunction after stroke

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Nanoscale neuro-anatomical determinants of synaptic strength, plasticity and integration

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Presynaptic plasticity in hippocampal circuits

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Structure and functions of the brain extracellular space

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The extracellular space of the brain: a multi-modal analysis from nano-structure to in vivo function

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News

Award of ERC Synergy Grant

 

 

 

 

Together with my Bordeaux colleagues (E. Bezard, L. Cognet and L. Groc), I am a proud recipient of an ERC Synergy grant from the EU, which supports high-risk/high gain frontier research in Europe. This is a tremendous recognition of our work, which will give us resources and wings to conduct some cool and ground-breaking research in the years to come! I am extremely grateful to all the members of my team and collaborators who have contributed to this success over the years and made it possible.

Selected Publications

  • Cassereau J, Courdavault V, Nägerl UV
  • Turning up the green light Trends in Cell Biology (2021)
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  • Arizono M, Bancelin S, Bethge P, Chéreau R, Idziak A, Inavalli VVGK, Pfeiffer T, Tønnesen J, Nägerl UV
  • Nanoscale imaging of the functional anatomy of the brain Neuroforum (2021)
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  • Arizono M, Inavalli VVGK, Bancelin S, Fernández-Monreal M, Nägerl UV
  • Super-resolution shadow imaging reveals local remodelling of astrocytic microstructures and brain extracellular space after osmotic challenge Glia (2021)
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  • Arizono M, Idziak A, Nägerl UV
  • It takes three to tango [Article in French] Médecine / Sciences (2021)
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  • Imig C, López-Murcia FJ, Maus L, García-Plaza IH, Mortensen LS, Schwark M, Schwarze V, Angibaud J, Nägerl UV, Taschenberger H, Brose N, Cooper BH.
  • Ultrastructural imaging of activity-dependent synaptic membrane-trafficking events in cultured brain slices Neuron (2020)
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  • Henneberger C, Bard L, Panatier A, Reynolds JP, Kopach O, Medvedev NI, Minge D, Herde MK, Anders S, Kraev I, Heller JP, Rama S, Zheng K, Jensen TP, Sanchez-Romero I, Jackson CJ, Janovjak H, Ottersen OP, Nagelhus EA, Oliet SHR, Stewart MG, Nägerl UV, Rusakov DA.
  • LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia Neuron (2020)
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  • Arizono M, Inavalli VVGK, Panatier A, Pfeiffer T, Angibaud J, Levet F, Ter Veer MJT, Stobart J, Bellocchio L, Mikoshiba K, Marsicano G, Weber B, Oliet SHR, Nägerl UV
  • Structural basis of astrocytic calcium signals at tripartite synapses Nature Communications (2020)
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  • Stolp B, Thelen F, Ficht X, Altenburger LM, Ruef N, Inavalli VVGK, Germann P, Page N, Moalli F, Raimondi A, Keyser KA, Seyed Jafari SM, Barone F, Dettmer MS, Merkler D, Iannacone M, Sharpe J, Schlapbach C, Fackler OT, Nägerl UV, Stein JV
  • Salivary gland macrophages and tissue-resident CD8+ T cells cooperate for homeostatic organ surveillance Science Immunology (2020)
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  • Levet F, Tønnesen J, Nägerl UV, Sibarita JB
  • SpineJ: A software tool for quantitative analysis of nanoscale spine morphology Methods (2020)
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  • Arizono M, Bancelin S, Nägerl UV
  • Thinking outside the cell: Super-resolution shadow imaging (SUSHI) of the extracellular space of the brain [Article in French] Médecine / Sciences (2020)
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  • Angibaud J, Mascalchi P, Poujol C, Nägerl UV
  • A simple tissue clearing method for increasing the depth penetration of STED microscopy of fixed brain slices Journal of Physics D: Applied Physics (2020)
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  • Inavalli VVGK , Lenz MO, Butler C, Angibaud J, Compans B, Levet F, Tonnesen J, Rossier O, Giannone G, Thoumine O, Hosy E, Choquet E, Sibarita JB, Nägerl UV
  • A super-resolution platform for correlative live single-molecule imaging and STED microscopy Nature Methods (2019)
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  • Denizot A, Arizono M, Nägerl UV, Soula H, Berry H
  • Simulation of calcium signaling in fine astrocytic processes: Effect of spatial properties on spontaneous activity PLoS Computational Biology (2019)
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  • Arizono M, Nägerl UV
  • ライブ超解像イメージングによる三者間シナプスのアストロサイト信号の解明 (Investigating astrocytic calcium signals at tripartite synapses using super-resolution microscopy) [Article in Japanese] Journal of Experimental Medicine (Jikken Igaku) (2019)
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  • Nägerl UV
  • Schattenriss des Gehirns [Article in German] Gehirn und Geist / Spektrum der Wissenschaft (2019)
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  • Hrabetova S, Cognet L, Rusakov DA, Nägerl UV
  • Unveiling the extracellular space of the brain: from super-resolved microstructure to in vivo function Journal of Neuroscience (2018)
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  • Pfeiffer T, Poll S, Bancelin S, Angibaud J, Inavalli VK, Keppler K, Mittag M, Fuhrmann M, Nägerl UV
  • Chronic 2P-STED imaging reveals high turnover of dendritic spines in the hippocampus in vivo eLife (2018)
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  • Tønnesen J, Inavalli VVGK, Nägerl UV
  • Super-resolution imaging of the extracellular space in living brain tissue Cell (2018)
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  • Chéreau R, Saraceno GE, Angibaud J, Cattaert D, Nägerl UV
  • Super-resolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity PNAS (2017)
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  • Panatier A, Arizono M, Nägerl UV
  • Dissecting tripartite synapses with STED microscopy Philos Trans R Soc Lond B Biol Sci (2014)
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  • Tønnesen J, Katona G, Rózsa B, Nägerl UV
  • Spine neck plasticity regulates compartmentalization of synapses Nature Neuroscience (2014)
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  • Bethge P, Chéreau R, Avignone E, Marsicano G, Nägerl UV
  • Two-photon excitation STED microscopy in two colors in acute brain slices Biophysical Journal (2013)
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    Members

    « Researcher »

    BANCELIN Stephane Researcher stephane.bancelin@u-bordeaux.fr +33533514745
    NÄGERL Valentin Researcher valentin.nagerl@u-bordeaux.fr +33533514707

    « Postdoc »

    ARIZONO Misa Postdoc misa.arizono@u-bordeaux.fr +33533514747
    MERCIER Luc Postdoc luc.mercier@u-bordeaux.fr +33533514745
    OKUDA Kosuke Postdoc kosuke.okuda@u-bordeaux.fr +33533514700

    « PhD student »

    IDZIAK Agata PhD student agata.idziak@u-bordeaux.fr +33533514750
    QUICI Federica PhD student federica.quici@u-bordeaux.fr +33533514750
    ROOS Johannes PhD student johannes.roos@u-bordeaux.fr +33533514750

    « Student »

    BELKADI Mohamed Student mohamed.belkadi@u-bordeaux.fr +33533514700
    NGUYEN Philippe Student philippe.nguyen@etu.u-bordeaux.fr +33533514700

    « Alumni & Guests »

    Visitors and guests (affiliation, position and dates)

    • Dr. Motohiro Nozumi (Nigata University, assistant professor, 06/2020 - 07/2021)
    • Dr. Yulia Dembitskaya (Collège de France, postdoc, 05 - 06/2021) 
    • Noemie Zerrouki (Université de Lille, undergrad internship student, 05/2021)
    • Prof. Sun Kim
    • Prof. Peter C. Kind
    • Dr. Angeles Almeida
    • Dr. Kohei Otomo
    • Dr. Julia Pinho
    • Dr. Nikolai Otmakhov

    Former team members (position at the time, dates, current position and contact)

    • Fabien Nadrigny (postdoc, June 2009 - 06/2011, high-school teacher)
    • Elena Avignone (assistant professor, 09/2009 - 09/2014, assistant professor, elena.avignone@u-bordeaux.fr)
    • Marion Jany (technician, 09/2011 - 09/2013)
    • Julie Angibaud (technician/lab engineer, 09/2010 - 12/2019, lab engineer/manager, julie.angibaud@u-bordeaux.fr)
    • Jan Tonnesen (postdoc, 09/2010 - 09/2016, group leader at Basque Center for Neuroscience, jan.tonnesen@ehu.eus)
    • Ronan Chereau (technician then PhD student, 09/2009 - 09/2015, postdoc at University of Geneva, ronan.chereau@unige.ch)
    • Phillip Bethge (PhD student, 09/2011-09/2014, lab manager at University of Zurich, bethge@hifo.uzh.ch)
    • Lasani Wijetunge
    • Marilyn Lepleux
    • Mirelle ter Veer
    • Krishna Inavalli
    • Martin Lenz
    • Lotte Razenberg
    • Richard Barrillet
    • Sandrine Pouvreau
    • Thomas Pfeiffer
    • Geraldine Louvet
    • Ezequiel Saraceno
    • Emanuele Murana
    • Cleopatre Djefal
    • Carlotta Pessina
    • Aude Panatier
    • Aleks Ichkova
    • Abdu Kuku  

     

     

    Jobs

    PhD position in Neurophotonics

    Qualifications: Background and interest in experimental physics, optics or engineering, and brain science, exceptional self-motivation, autonomy and creativity and team player

    Offer:  PhD project in the Nägerl team at the cutting-edge interface of optical method development, super-resolution microscopy and neuroscience, embedded in the graduate program EUR Light S&T and Bordeaux Neurocampus at the University of Bordeaux.

    References:

    How to apply? Email i) a cover letter explaining your interests and motivation, ii) CV, and iii) a reference letter to: Prof. Dr. U. Valentin Nägerl (valentin.nagerl@u-bordeaux.fr).

    Research engineer position in Neurophotonics for ERC project

    The Nägerl team is recruiting a research engineer/lab tech/postdoc (depending on qualifications) to help build, improve, test and run new optical microscopy techniques, with a special focus on super-resolution fluorescence microscopy.

    The task is to optimize and apply them to living mouse brain tissue and in vivo.

    You will implement, develop and use state-of-the-arts and innovative fluorescence labeling approaches, sample preparation, custom-designed illumination and light detection schemes and (computational) data analysis. You will work together with other team members and assist them in tackling the technical challenges.

    high affinity for technology and all things optical is a must, troubleshooting, tinkering and general resourcefulness and ingenuity. Programming skills (Python/Matlab/LabView) is a plus, as well as a deep curiosity about the mysteries of biological phenomena and mechanisms.

    The goal is to visualize dynamic cellular brain structures and processes, to see them more clearly and directly, more inclusively and contextually, faster and deeper, less invasively and less tediously so.

    Beyond registering exciting new observations, we want to make neurobiological sense out of them. To help decrypt the wonders of synapses, neurons and the brain, nothing less!

    The job is part of a ERC-Synergy project with a long-term perspective and a thriving and dynamic workplace environment in a major European research and training center for neuroscience and  photonics.

    Contact: valentin.nagerl@u-bordeaux.fr

    Fundings