bordeaux school of neuroscience march 23 to april 10, 2020 ... files/cajal/2020/aitcsn/key… ·...

CAJAL Neuroscience Training Course

Advanced imaging techniques for cellular and systems in neuroscience Bordeaux School of Neuroscience – March 23 to April 10, 2020

The CAJAL Advanced Neuroscience Training Programme www.cajal-training.org

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Keynote-speakers

Thomas BLANPIED, PhD | University of Maryland School of Medicine, USA

I graduated from Yale University with a bachelor's degree in Psychology. My long-standing interest in cognition and learning has lead to my current work to understand the cellular processes that underlie mental health and psychiatric disorder. At the University of Pittsburgh, I obtained a Ph.D. in the Department of Neuroscience with Jon Johnson, Ph.D., where I used single-channel recordings to study the mechanisms by which the anti-Parkinsonian and anti-Alzheimer's drugs amantadine and memantine act on NMDA receptors. I then undertook postdoctoral training with George

Augustine, Ph.D. and Michael Ehlers, M.D. Ph.D. at Duke University in the Department of Neurobiology. I joined the Department as an Assistant Professor in 2005, and was promoted to Associate Professor with tenure in 2012. Selected publications: - Divakaruni SS, Van Dyke AM, Chandra R, LeGates TA, Contreras M, Dharmasri PA, Higgs HN,

Lobo MK, Thompson SM,Blanpied TA. (2018) Long-Term Potentiation Requires a Rapid Burst of

Dendritic Mitochondrial Fission during Induction. Neuron in press.

- Biederer T, Kaeser PS, Blanpied TA. (2017) Transcellular Nanoalignment of Synaptic Function.

Neuron. 96:680-696.

- Francis TC, Chandra R, Gaynor A, Konkalmatt P, Metzbower SR, Evans B, Engeln M, Blanpied

TA, Lobo MK. (2017) Molecular basis of dendritic atrophy and activity in stress susceptibility. Mol

Psychiatry. 22:1512-1519.

- Tang AH*, Chen H*, Li TP, Metzbower SR, MacGillavry HD, Blanpied TA. (2016) A trans-synaptic

nanocolumn aligns neurotransmitter release to receptors. Nature 535 (7215) August 11. (*These

authors contributed equally.)

- Li TP and Blanpied TA. (2016) Control of Transmembrane Protein Diffusion within the

Postsynaptic Density Assessed by Simultaneous Single-Molecule Tracking and Localization

Microscopy. Frontiers in Synaptic Neuroscience 8: 8-22-16.

- Perez de Arce K, Schrod N, Metzbower SR, Kong G K-W, Tang A, Krupp AJ, Stein V, Liu X,

Blanpied TA, Lucic V and Biederer T. (2015) Topographic Mapping of the Synaptic Cleft into

Adhesive Nanodomains. Neuron 88(6): 1165–1172.

- Lu HE, MacGillavry HD, Frost NA, Blanpied TA (2014) Multiple spatial and kinetic

subpopulations of CaMKII in spines and dendrites as resolved by single-molecule tracking PALM.

J Neurosci. 2014 May 28;34(22):7600-10

- MacGillavry, HD, Song, Y, Raghavachari, S, and Blanpied TA. (2013) Nanoscale scaffolding

domains within the postsynaptic density concentrate synaptic AMPA receptors. Neuron. 78: 615-

22.

http://www.cajal-training.org/




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Daniel CHOQUET, PhD | University of Bordeaux (Bordeaux Neurocampus), France

Daniel Choquet obtained an engineering degree from Ecole Centrale (Paris, France) in 1984. He then got attracted to neuroscience and completed his PhD in the lab of Henri Korn at the Pasteur Institute (Paris), studying ion channels in lymphocytes. He got appointed tenure Research officer at the CNRS in 1988. He then performed a post-doctoral/sabbatical at the Duke University (North Carolina, USA) in the laboratory of Michael Sheetz where he studied the regulation of integrin-cytoskeletal linkage by force, and demonstrated that cells can sense and respond to extracellular traction. He then setup his

group in Bordeaux (France) at the Institute for Neuroscience where he got a directorship position at the CNRS. He launched an interdisciplinary program on the combination of physiology, cell and chemical biology and high resolution imaging to study the functional role of the dynamic organization and trafficking of neurotransmitter receptors in synaptic transmission. He is now heading the Institute for Interdisciplinary Neuroscience and the Bordeaux Imaging Center core facility. He is also the director of the center of excellence BRAIN, Bordeaux Region Aquitaine Initiative for Neuroscience. He has been the recipient of several awards including the 1990 Bronze Medal from the CNRS, the Research prize from the Fondation pour la Recherche Médicale (FRM), 1997, the Grand Prix from the French Academy of Sciences, Prix du CEA and the 2009 Silver Medal from the CNRS. He is a Member of the Institut de France, the French Science Academy since November 2010 and Officier de la Légion d’honneur. He has been awarded three ERC advanced grants in 2008, 2013 and 2018. His team develops several research topics, combining neuroscience, physics and chemistry in order to unravel the dynamics and nanoscale organization of multimolecular receptor complexes and their functional role in glutamatergic synaptic transmission. Recently, the team has engaged in a major program to analyse and understand the interplay between AMPA type glutamate receptor nanoscale dynamics, synaptic plasticity and memory formation in the healthy and diseased brain. Selected publications: - Linking Nanoscale Dynamics of AMPA Receptor Organization to Plasticity of Excitatory Synapses

and Learning. Choquet D. J Neurosci. 2018 Oct 31;38(44):9318-9329. - Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in

Huntington's disease models. Zhang H, Zhang C, Vincent J, Zala D, Benstaali C, Sainlos M, Grillo-Bosch D, Daburon S, Coussen F, Cho Y, David DJ, Saudou F, Humeau Y, Choquet D.

- Nat Commun. 2018 Oct 15;9(1):4272 - CaMKII Metaplasticity Drives Aβ Oligomer-Mediated Synaptotoxicity. Opazo P, Viana da Silva S,

Carta M, Breillat C, Coultrap SJ, Grillo-Bosch D, Sainlos M, Coussen F, Bayer KU, Mulle C, Choquet D. Cell Rep. 2018 Jun 12;23(11):3137-3145

- Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95. Hafner AS, Penn AC, Grillo-Bosch D, Retailleau N, Poujol C, Philippat A, Coussen F, Sainlos M, Opazo P, Choquet D. Neuron. 2015 Apr 22;86(2):475-89.

Rosa COSSART, PhD | Aix-Marseille University, France

More to come…





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Olga GARASCHUK, PhD | University of Tübingen, Germany

Olga Garaschuk holds the Chair for Neurophysiology (W3) at the Eberhard Karls University of Tübingen since 2008. She is an elected member of Academia Europaea, a Member of the scientific advisory board of the Center of Advanced European Studies and Research (Bonn), the scientific advisory board of the Bernstein Centre for Computational Neuroscience and Bernstein Fokus Neurotechnology (Göttingen University) and a Mentor at the "Helmholtz Management Academy". Her research (supported by e.g. DFG, VolkswagenStiftung, Alexander von Humboldt-Stiftung and Horizon 2020) focuses

on (i) functional analysis of neuronal networks in vivo, especially in context of perception of sensory stimuli; (ii) interactions between the nervous and the immune systems of the brain as well (iii) aging and neurodegeneration (in particular, Alzheimer disease). Among her scientific achievements is development of several techniques for functional in vivo imaging of neural networks, pioneering research on in vivo Ca2+-signaling in microglia as well as adult neural stem cells. Olga Garaschuk graduated in physico-chemical biology from the Moscow Institute for Physics & Technology (MFTI) with top honors. She gained her PhD at the Bogomoletz Institute for Physiology in Kyiv in 1992, and moved first to the Max Planck Institute for Biophysical Chemistry in Gottingen and thereafter to the Institute of Physiology at the University of Saarland, where she was awarded the Irène Curie habilitation Scholarship. She habilitated in Physiology at the Ludwig-Maximilians University, Munich in 2003. Before moving to Tübingen Olga Garaschuk was appointed as Professor for Neuroimaging (W2) at the Institute of Neuroscience of the Technical University in Munich (2006). Since 2016 Olga Garaschuk is a president of the German-Ukrainian Academic Society. She was born in Kyiv, Ukraine, is married and has three daughters. Selected publications (86 in total, Times cited: 6117 (Scopus) h-index 32, cumulative IF: 501.54) - Lerdkrai C., Asavapanumas N., Brawek B., Kovalchuk Y., Mojtahedi N., Olmedillas del Moral M.,

Garaschuk O. 2018 Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer’s disease. PNAS USA 115: E1279-E1288.

- Liang Y, Li K., Riecken K, Maslyukov A, Gomez-Nicola D, Kovalchuk Y, Fehse B, Garaschuk O. 2016 Long-term in vivo single cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb. Cell Research 26: 805-821.

- Kovalchuk Y, Homma R, Liang Y, Maslyukov A, Hermes M, Thestrup T, Griesbeck O, Ninkovic J, Cohen LB, Garaschuk O. 2015 In vivo odorant response properties of migrating adult-born neurons in the mouse olfactory bulb. Nature Communications 6, 6349.

- Brawek B, Schwendele B, Riester K, Kohsaka S, Lerdkrai C, Liang Y, Garaschuk O. 2014 Impairment of in vivo calcium signaling in amyloid plaque-associated microglia. Acta Neuropathol. 127, 495-505.

- Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, Staufenbiel M, Konnerth A, Garaschuk O. 2008 Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer’s disease. Science 321: 1686-1689.


http://www.ncbi.nlm.nih.gov/pubmed/24407428




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Laurent GROC, PhD | University of Bordeaux (Bordeaux Neurocampus), France

Laurent Groc identified a form of glutamate receptor plasticity in immature synapses as a post-doc with Eric Hanse (Goteborg, Sweden). Laurent then explored glutamate receptor trafficking in developing neurons using single molecule tracking and electro-physiology. He currently heads a lab at the Interdisciplinary Institute for Neuroscience in Bordeaux1,2, focusing on receptor dynamics in developing networks. He will instruct single nanoparticle tracking of membrane receptors in developing neurons.

Selected publications : - Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at

Glutamatergic Synapses. Kellermayer B, Ferreira JS, Dupuis J, Levet F, Grillo-Bosch D, Bard L, Linarès-Loyez J, Bouchet D, Choquet D, Rusakov DA, Bon P, Sibarita JB, Cognet L, Sainlos M, Carvalho AL, Groc L. Neuron 2018. doi: 10.1016/j.neuron.2018.09.012.

- Pathogenicity of Antibodies against NMDA Receptor: Molecular Insights into Autoimmune Psychosis. Jézéquel J, Johansson EM, Leboyer M, Groc L. Trends Neurosci. 2018. doi: 10.1016/j.tins.2018.05.002.

- Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients. Jézéquel J, Johansson EM, Dupuis JP, Rogemond V, Gréa H, Kellermayer B, Hamdani N, Le Guen E, Rabu C, Lepleux M, Spatola M, Mathias E, Bouchet D, Ramsey AJ, Yolken RH, Tamouza R, Dalmau J, Honnorat J, Leboyer M, Groc L. Nat Commun. 2017. doi: 10.1016/j.tins.2018.05.002.

- Cell- and Single Molecule-Based Methods to Detect Anti-N-Methyl-D-Aspartate Receptor Autoantibodies in Patients With First-Episode Psychosis From the OPTiMiSE Project. Jézéquel J, Rogemond V, Pollak T, Lepleux M, Jacobson L, Gréa H, Iyegbe C, Kahn R, McGuire P, Vincent A, Honnorat J,

Michael HÄUSSER, PhD | University College London, UK

Michael Häusser is Professor of Neuroscience at University College London and a Principal Research Fellow of the Wellcome Trust. He did his PhD work at Oxford University under the supervision of Julian Jack. He subsequently worked with Bert Sakmann at the Max-Planck-Institute for Medical Research in Heidelberg and with Philippe Ascher at the Ecole Normale Superieure in Paris. He established his own lab at UCL in 1997, where his group aims to understand the cellular basis of neural computation in the mammalian brain using a combination of experiments and theory, with a special focus

on the role of dendrites. He is also the Facilitator of the International Brain Laboratory (www.internationalbrainlab.com), a new global open-science collaboration which aims to understand how the brain makes decisions. Lab website: www.dendrites.org Selected publications: - Smith, S., Smith, I.T., Branco, T., Häusser, M. (2013). Dendritic spikes enhance stimulus selectivity

in cortical neurons in vivo. Nature 503(7474):115-20.


https://www.ncbi.nlm.nih.gov/pubmed/29176681

https://www.ncbi.nlm.nih.gov/pubmed/29176681

http://www.dendrites.org/




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- Packer A.M., Russell L.E., Dalgleish H.W., Häusser M. (2015). Simultaneous all-optical manipulation and recording of neural circuit activity with cellular resolution in vivo. Nature Methods 12(2):140-6.

- Schmidt-Hieber C, Toleikyte G, Aitchison L, Roth A, Clark BA, Branco T, Häusser M (2017). Active dendritic integration as a mechanism for robust and precise grid cell firing. Nature Neuroscience 20(8):1114-1121.

- Zhang Z, Russell LE, Packer AM, Gauld OM, Häusser M (2018). Closed-loop all-optical interrogation of neural circuits in vivo. Nature Methods 15(12):1037-1040.

- Kostadinov D, Beau M, Pozo MB, Häusser M (2019). Predictive and reactive reward signals conveyed by climbing fiber inputs to cerebellar Purkinje cells. Nature Neuroscience 22(6):950-962.

Christian HENNEBERGER, PhD | University of Bonn, Germany

Christian Henneberger is a Professor for Neurophysiology at the University of Bonn in the Institute of Cellular Neurosciences. He was trained in Germany at the Humboldt University Berlin and in the United Kingdom at the University College London in the labs of Rosemarie Grantyn and Dmitri Rusakov. His main scientific interest are the mechanisms of synaptic transmission and plasticity and how they are shaped by signal exchange with glial cells and by the geometry of the tripartite synapse. Recent work of his lab investigates the mechanisms by which neurons and astrocytes supply the

NMDA receptor (NMDAR) co-agonists D-serine and glycine and thus govern NMDAR-dependent synaptic plasticity in the hippocampus. In collaboration with Colin Jackson’s lab (ANU, Canberra) his lab is developing novel optical sensor for these co-agonists and uses them to investigate the spatiotemporal dynamics of co-agonist signalling. In the course, Christian will introduce in situ imaging of extracellular neurotransmitter dynamics. Selected publications: - Zhang WH, Herde MK, Mitchell JA, Whitfield JH, Wulff AB, Vongsouthi V, Sanchez-Romero I,

Gulakova PE, Minge D, Breithausen B, Schoch S, Janovjak H, Jackson CJ, Henneberger C (2018) Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS. Nat. Chem. Biol. 14(9):861-869.

- Minge D, Senkov O, Kaushik R, Herde MK, Tikhobrazova O, Wulff AB, Mironov A, van Kuppevelt TH, Oosterhof A, Kochlamazashvili G, Dityatev A, Henneberger C (2017) Heparan sulfates support pyramidal cell excitability, synaptic plasticity and context discrimination. Cereb. Cortex 27(2):903-918.

- Anders S, Minge D, Griemsmann S, Herde MK, Steinhäuser C, Henneberger C (2014) Spatial properties of astrocyte gap junction coupling in the rat hippocampus. Phil. Trans. R. Soc. B 369(1654):20130600.

- Henneberger C, Papouin T, Oliet SHR, Rusakov DA (2010). Long-term potentiation depends on release of d-serine from astrocytes. Nature 463: 232-236.

- Kochlamazashvili G*, Henneberger C*, Bukalo O*, Dvoretskova E, Senkov O, Lievens PM, Westenbroek R, Engel AK, Catterall WA, Rusakov DA, Schachner M, Dityatev A. (2010) The Extracellular Matrix Molecule Hyaluronic Acid Regulates Hippocampal Synaptic Plasticity by Modulating Postsynaptic L-Type Ca2+ Channels. Neuron 67: 116-128. (* equal contribution)





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Christophe LETERRIER, PhD | Aix-Marseille University, Germany

Christophe Leterrier has been working on the organization of the axon since his PhD with Zsolt Lenkei in Paris, where he studied the axonal targeting of the CB1 cannabinoid receptor. For his postdoc in Bénédicte Dargent's lab in Marseille, he worked on revealing new cytoskeletal components of the axon initial segment, as well as their nanoscale organization. He started the NeuroCyto lab in 2017, with the aim of deciphering the axonal cytoskeleton architecture using advanced microscopy techniques. The team currently focuses the organization of axonal actin and its partners in order to

understand the function of newly discovered axonal actin structures: rings, hotspots and trails. Selected publications: - The functional architecture of axonal actin. Papandréou MJ, Leterrier C. Mol Cell Neurosci. 2018

Sep;91:151-159. - Quantitative mapping and minimization of super-resolution optical imaging artifacts. Culley S,

Albrecht D, Jacobs C, Pereira PM, Leterrier C, Mercer J, Henriques R. Nat Methods. 2018 Apr;15(4):263-266.

- The nano-architecture of the axonal cytoskeleton. Leterrier C, Dubey P, Roy S. Nat Rev Neurosci. 2017 Dec;18(12):713-726.

- A dynamic formin-dependent deep F-actin network in axons. Ganguly A, Tang Y, Wang L, Ladt K, Loi J, Dargent B, Leterrier C, Roy S., J Cell Biol. 2015 Aug 3;210(3):401-17.

Valentin NÄGERL, PhD | University of Bordeaux (Bordeaux Neurocampus), France

Valentin Nägerl was trained in Germany, working with Tobias Bonhoeffer, Arthur Konnerth and the Nobel laureate Stefan Hell. He made several crucial observations on how structural changes in the postsynaptic spine contribute to synaptic plasticity. Valentin is now a full professor of neuroscience and bio-imaging at the University of Bordeaux and continues to study the nanoscale structural mechanisms of neural plasticity using super-resolution imaging. In the course, Valentin will instruct spine motility in living neurons using STED microscopy.

Selected publications: - Chéreau et al. (2017) PNAS Feb 7;114(6):1401-1406. - Tønnesen et al. (2014) Nat Neurosci. 17:678-85. - Becker et al. (2008) Neuron 60:590-7. - Nägerl et al. (2004) Neuron 44:759-67.





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Timothy A. RYAN, PhD | Weill Cornell Medical College, USA

Timothy Ryan is a Rockefeller/Sloan-Kettering/Cornell Tri-Institutional Professor in the department of Biochemistry at Weill Cornell Medical College and a Senior fellow at the Howard Hughes Medical Institute Janelia Research Campus. He received his BSc with honors in Physics at McGill University and his PhD in Physics at Cornell University. He carried out postdoctoral work at Stanford University in the department of Molecular and Cellular Physiology. Dr. Ryan’s lab has pioneered the development and use of quantitative optical tools to interrogate nerve terminal function. He was an Alfred

P. Sloan Fellow, a two-time recipient of the McKnight Technological Innovations in Neuroscience Award, a recipient of the NINDS Javits Award and a recipient of the Siegel Family Award for Outstanding Biomedical Research. Selected publications:

- V. Rangaraju, N. Calloway & T. A. Ryan. Activity-driven local ATP synthesis is required for

synaptic function. Cell (2014) 156(4):825-35.

- M. Hoppa, G. Gouzer, M. Armbruster & T. A. Ryan. Control and plasticity of the presynaptic

action potential waveform at small CNS nerve terminals. Neuron (2014) 84(4):778-789

- G. Ashrafi, Z. Wu, R.J. Farrell & T. A. Ryan. Glut4 mobilization supports energetic demands

of active synapses. Neuron (2017) 93(3):606-615.e3. doi: 10.1016.

- J. de Juan Sanz, G. T. Holt, F. de Juan, D. S. Kim & T. A. Ryan. Axonal endoplasmic reticulum

Ca2+ content controls release probability in CNS nerve terminals. Neuron (2017)

93(4):867-881.e6. doi: 10.1016/j.neuron.2017.01.010

- G. Ashrafi, J. de Juan Sanz, R. Farrell & T. A. Ryan. Molecular tuning of the axonal

mitochondrial Ca2+ uniporter ensures metabolic flexibility of neurotransmission. Neuron

(2019) in press

Ilaria TESTA, PhD | KTH Royal Institute of Technology, Sweden

I performed my PhD between 2006 and 2009 at the University of Genoa (Italy) in the group of Professor Alberto Diaspro working on the use of Photoswitchable Fluorescent Proteins in two photon microscopy for functional analysis in living cells. Between 2009-2014 I worked as a Postdoc Researcher at the Department of NanoBiophotonics directed by Professor Stefan Hell at the Max Planck Institute for Biophysical Chemistry in Göttingen (Germany). During this time I actively designed and developed several nanoscopes that implement two different approaches for achieving super-resolution

imaging: (1) the first set-up was based on stochastic switching of single molecule between a fluorescent and a non-fluorescent state (GSDIM/PALM/STORM) with multicolour ability based on ratiometric detection (2) the second set-up showed the practical accomplishment of RESOLFT, a target switching technique based on reversible long lived molecular transition. Within an interdisciplinary team of biologists and physicists we succeeded to demonstrate





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RESOLFT in living cells and even tissues. Since 2015 I’m conducting my independent research at the Science for Life Laboratory as Faculty at the Royal Institute of Technology (KTH, Stockholm, Sweden). The goal of my group is to develop the novel paradigms made available by super-resolution microscopy to address contemporary challenges in biophysics and neuroscience. To achieve this goal we push forward the quantitative aspect of live cell imaging by setting-up and applying different concepts of super-resolution microscopy based on target switching such as automated STED microscopy. We developed two new nanoscopes named MoNaLISA and smart RESOLFT which allow the precise identification of populations of neuronal proteins and organelles depending on their localization, abundance and dynamics inside their native environment. We also use our technology to investigate neuronal proteins, especially in synapses, where trafficking organelles and protein complexes are so tight in space that resolving them requires high resolution in space and time. Selected publications: - Jes Dreier, Marco Castello, Giovanna Coceano, Rodrigo Cáceres, Julie Plastino, Giuseppe Vicidomini

and Ilaria Testa, “Smart scanning for low-illumination and fast RESOLFT nanoscopy in vivo” Nature Communications, volume 10, Article number: 3281.

- Luciano A. Masullo*, Andreas Bodén*, Francesca Pennacchietti*, Giovanna Coceano, Michael Ratz and Ilaria Testa (2018) Enhanced photon collection enables four dimensional fluorescence nanoscopy of living systems. Nature Communications, volume 9, Article number: 3281

- Francesca Pennacchietti*, Ekaterina O. Serebrovskaya*, Aline R. Faro*, Irina I. Shemyakina*, Nina G. Bozhanova, Alexey A. Kotlobay, Nadya G. Gurskaya, Andreas Bodén, Jes Dreier, Dmitry M. Chudakov, Konstantin A. Lukyanov, Vladislav V. Verkhusha, Alexander S. Mishin and Ilaria Testa. (2018) Fast reversibly photoswitching red fluorescent proteins for live-cell RESOLFT nanoscopy Nature Methods 15, 601–604

- Ilaria Testa, Nicolai T. Urban, Stefan Jakobs, Christian Eggeling, Katrin I. Willig, Stefan W. Hell (2012) Nanoscopy of living brain slice with low light levels, Neuron 75: 992–1000 doi: 10.1016/j.neuron.2012.07.028

Andrea VOLTERRA, PhD | University of Lausanne, Switzerland

Andrea Volterra, Italian, 62 years-old, is Full Professor at the Department of Fundamental Neurosciences, University of Lausanne, Switzerland since 2001, which he directed from 2004 to 2012. He obtained a PhD in Pharmacology from Univ Milan, Italy (1985), joined the labs of Steven Siegelbaum and the Nobel Prize Eric Kandel at Columbia University, New York, as Research Scientist (1986-89) and then started his independent career as Assistant and then Associate Professor at the Dept. Pharmacology, Univ Milan (19902000). In 2001 he moved to Switzerland. He is member of Academia Europea

and Swiss Academy of Medical Sciences (SAMS), and of Swiss, European and American Societies of Neuroscience, and won several prices, including the Theordore Ott price 2017 from SAMS. Prof. Volterra obtained >30 grants as PI, including currently, the prestigious ERC Advanced, Swiss National Science Foundation individual grant and participates in two of the Swiss National Centers of Excellence (NCCRs), “Transcure” and “Synapsy”. He is author of 125 publications with >10000 citations and h-index of 42 (Thomas Reuters’ Web of Science). His research field is astrocyte-neuron communication and its contribution to synaptic integration





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and the pathogenesis of neuropsychiatric disorders, to which he contributed some of the seminal work in the last twenty years. Initially he worked in the field of biochemical neuropsychopharmacology; at Columbia University studied memory paradigms in Aplysia Californica with electrophysiology techniques (Piomelli et al., Nature, 1987; Buttner et al., Nature, 1989; Sweatt et al., Nature, 1989). Between 1990 and 2000 focused on the role of glutamate transport in physiology and disease. In 1997-2001 he discovered a Ca2+-dependent pathway of transmitter release from astrocytes and demonstrated its role in synaptic function and pathology (Bezzi et al., Nature, 1998; Bezzi et al. Nature Neurosci, 2001). In the last 18 years, his research has widened up from the initial discoveries to establish his group as one of the pioneers in deciphering the modulatory role of astrocytes in synaptic function via the release of neuroactive messengers and in showing that perturbation of this astrocyte input to synapses causes neuronal damage, supporting the idea of non-cell autonomous mechanisms of neuronal degeneration, possibly one of the key advances in neurology in recent years (Bezzi et al., Nature Neurosci, 2004; Jourdain et al. Nature Neurosci., 2007; Di Castro et al., Nature Neurosci., 2011; Santello et al., Neuron, 2011; Habbas et al., Cell 2015; Bindocci et al., Science, 2017; reviewed in Volterra and Meldolesi, Nature Rev Neurosci., 2005 and recently in Araque et al., Neuron, 2014 and Volterra et al., Nature Review Neurosci., 2014; Santello et al., Nature Neurosci 2019). His most recent work, using a multidisciplinary approach and novel imaging technologies, is engaged in decoding the language of astrocytes in cognitive function and dysfunction. Selected publications: - Savtchouk I, Carriero G, Volterra A. Studying Axon-Astrocyte Functional Interactions by 3D Two-

Photon Ca(2+) Imaging: A Practical Guide to Experiments and "Big Data" Analysis. Front Cell

Neurosci. 2018 Apr 13;12:98. doi: 10.3389/fncel.2018.00098. eCollection 2018. PubMed PMID:

29706870; PubMed Central PMCID: PMC5908897.

- Bindocci E, Savtchouk I, Liaudet N, Becker D, Carriero G, Volterra A. Three-dimensional Ca(2+)

imaging advances understanding of astrocyte biology. Science. 2017 May 19;356(6339). pii:

eaai8185. doi: 10.1126/ science.aai8185. PubMed PMID: 28522470.

- Volterra A, Liaudet N, Savtchouk I. Astrocyte Ca²⁺ signalling: an unexpected complexity. Nat Rev

Neurosci. 2014 May;15(5):327-35. doi: 10.1038/ nrn3725. Review. PubMed PMID: 24739787.

- Di Castro MA, Chuquet J, Liaudet N, Bhaukaurally K, Santello M, Bouvier D, Tiret P, Volterra A. Local

Ca2+ detection and modulation of synaptic release by astrocytes. Nat Neurosci. 2011 Sep

11;14(10):1276-84. doi: 10.1038/ nn.2929. PubMed PMID: 21909085.

- Habbas S, Santello M, Becker D, Stubbe H, Zappia G, Liaudet N, Klaus FR, Kollias G, Fontana A,

Pryce CR, Suter T, Volterra A. Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling.

Cell. 2015 Dec 17;163(7): 1730-41. doi: 10.1016/j.cell.2015.11.023. Epub 2015 Dec 10. PubMed

PMID:26686654





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Kirill VOLYNSKI, PhD | University College London, UK

Kirill Volynski is a Professor of Neuroscience at UCL Queen Square Institute of Neurology. His research is focused on understanding the mechanisms of Ca2+-dependent regulation of transmitter release at the level of individual presynaptic boutons. His group established a powerful suite of quantitative fluorescence microscopy methods in neuronal cultures (Ermolyuk et al., 2013;Ermolyuk et al., 2012;Novak et al., 2013). This resulted in the discovery that two equally important mechanisms contribute to the basal heterogeneity of neurotransmitter release probability: the size of the readily

releasable pool of vesicles, which scales with bouton size, and the fusion probability of individual release-ready vesicles, which in turn is determined by the size of the AP-evoked Ca2+ influx (Ermolyuk et al., 2012). Using combination of electrophysiology and computational modelling Volynski lab showed that stochastic opening of individual Ca2+ channels contributes to both evoked and spontaneous glutamate release (Ermolyuk et al., 2013). In collaboration with Y. Korchev (Imperial College London) he has obtained the first nanoscale-targeted patch-clamp recordings from small presynaptic boutons and applied this unique methodology to understand the presynaptic mechanisms of episodic ataxia type 1 which is caused by mutations in Kv1.1 potassium channel (Novak et al., 2013;Vivekananda et al., 2017). Selected publications: - Ermolyuk,Y.S., Alder,F.G., Surges,R., Pavlov,I.Y., Timofeeva,Y., Kullmann,D.M., and Volynski,K.E.

(2013). Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca(2+)

channels. Nat. Neurosci. 16, 1754-1763.

- Ermolyuk,Y.S., Alder,F.G., Henneberger,C., Rusakov,D.A., Kullmann,D.M., and Volynski,K.E. (2012).

Independent Regulation of Basal Neurotransmitter Release Efficacy by Variable Ca<sup>2+</sup>

Influx and Bouton Size at Small Central Synapses. PLoS Biol 10, e1001396.

- Novak,P., Gorelik,J., Vivekananda,U., Shevchuk,A.I., Ermolyuk,Y.S., Bailey,R.J., Bushby,A.J.,

Moss,G.W., Rusakov,D.A., Klenerman,D., Kullmann,D.M., Volynski,K.E., and Korchev,Y.E. (2013).

Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels. Neuron 79,

1067-1077.

- Vivekananda,U., Novak,P., Bello,O.D., Korchev,Y.E., Krishnakumar,S.S., Volynski,K.E., and

Kullmann,D.M. (2017). Kv1.1 channelopathy abolishes presynaptic spike width modulation by

subthreshold somatic depolarization. Proc. Natl. Acad. Sci. U. S. A. 114, 2395-2400.


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