Cajal BNHC keynote speakers - FENS.org Gallery/CAJAL programme/2… ·...

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

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Cajal course on Biosensors and Actuators for Cellular and Systems Neuroscience

Keynote Speakers

Ryohei Yasuda, PhD (Max Planck Florida Institute for Neuroscience) Dr. Ryohei Yasuda received his Ph.D. in physics in 1998 from Keio University Graduate School of Science and Technology in Yokohama, Japan. In his Ph.D. study, he demonstrated that the enzyme ATP synthase is a rotary motor made of single molecule and that its energy conversion efficiency is close to 100%. From 2000 to 2005, he was a post-‐doctoral fellow at the Cold Spring Harbor Laboratory, where he built an imaging device to monitor protein interactions in living cells with high sensitivity and resolution. From 2005 to 2012, he was an assistant professor of the Neurobiology department at the Duke University Medical Center, where he developed a number of techniques to visualize signaling activity in single synapses. From 2009 to 2012, he also served as an Early Career Scientist at the Howard Hughes Medical Institute. In 2012, Dr. Yasuda was named Scientific Director of the Max Planck Florida Institute for Neuroscience. His current focus is to elucidate molecular mechanisms underlying synaptic plasticity and ultimately, learning and memory. He has received a number of awards for his research accomplishments including: the Career Award at the Scientific Interface from the Burroughs Wellcome Fund; the Alfred P. Sloan Fellowship; the New Investigator Award from the Alzheimer's Association; and the Research Award for Innovative Neuroscience from the Society for Neuroscience. Selected Publications:

- PKCα integrates spatiotemporally distinct Ca2+ and autocrine BDNF signaling to facilitate synaptic plasticity. Colgan, L.A., et al (2018). Nature Neuroscience. Online Publication.

- An open-‐source tool for analysis and automatic identification of dendritic spines using machine learning. Smirnov, M.S., et al. (2018). PLOS ONE. Online Publication.

- RGS14 Restricts Plasticity in Hippocampal CA2 by Limiting Postsynaptic Calcium Signaling. Evans, P.R., et al. (2018). ENeuro ENEURO.0353-‐17.2018.

- Biophysics of Biochemical Signaling in Dendritic Spines: Implications in Synaptic Plasticity. Yasuda, R. (2017). Biophysical Journal 113, 1-‐8.

Scott Sternson, PhD (Janelia farm, HHMI) Scott received his PhD in Chemistry from Harvard University, working with Stuart Schreiber on the synthesis and development of new probes to manipulate cellular function. After realizing a desire to work on a fundamental behavioral problem using molecular genetics integrated with neurophysiology, he did a postdoc with Jeff Friedman at Rockefeller University and also worked in Karel Svoboda’s lab (then at Cold Spring Harbor) to map molecularly-‐defined neural circuits regulating feeding behavior. At Janelia, Scott has been focused on understanding the circuit mechanisms underlying basic motivations such as hunger.


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Selected Publications:

- Chemogenetic tools for causal cellular and neuronal biology. Atasoy D, et al. (2017) Physiological Reviews. Dec 12

- Raphe circuits on the menu. Yang H, Sternson SM. (2017) Cell. Jul 27;170(3):409-‐10.

- Three pillars for the neural control of appetite. Sternson SM, Eiselt A (2016) Annual Review of Physiology. 2016 Nov 28;79:401-‐23.

- Near-‐perfect synaptic integration by Nav1.7 in hypothalamic neurons regulates body weight. Branco T, et al. (2016) Cell. Jun 16;165(7):1749-‐61.

Olivier Griesbeck, PhD (Max-‐Planck-‐Institute of Neurobiology, Martinsried)

Oliver Griesbeck got his Degree in Genetics and Biochemistry from Ludwig-‐Maximilian-‐University,Munich in 1993. He finished his PhD in 1997 in Neurobiology at Max-‐Planck-‐Institute for Psychiatry at the Department of Neurochemistry in Martinsried. He was a Research Associate of the Howard Hughes Medical Institute, University of California, San Diego, with Roger Y. Tsien from 1997-‐2001. Since 2011 he is a Research Group leader at the Department of Systems and Computational Neurobiology, Max-‐Planck-‐Institute of Neurobiology, Martinsried. His research is an example of cross disciplinary innovation which pushes

neuroscience forward. One of the greatest challenges in neuroscience has been to monitor activity and biochemistry in populations of identified neurons in vivo and to relate their activity patterns to behaviour. Previous work on new microscopy techniques has moved the field considerably further in that direction. In particular the combination of modern imaging technology and genetic labeling methods heralds a bright future for neuronal circuit analysis. His work complements these efforts on the “indicator side” by providing probes for key events crucial for an understanding of neuronal function and plasticity and aims at overcoming long-‐standing limitations in the ability to monitor neuronal activity and biochemistry in intact tissues. His approach is the design and engineering of genetically encoded biosensors, from the cuvette via imaging of single cells in culture to the generation of whole transgenic indicator organisms which harbor the biosensor of choice in the cells and tissues that one wishes to study. This opens up new avenues for the study of structure-‐function relationships of intact neuronal circuits. Selected Publications:

- Imaging-‐based screening platform assists protein engineering Fabritius A, et al (2018). Cell Chem. Biol. 25: 1-‐8

- Color Processing in the Early Visual System of Drosophila. Schnaitmann C, (2018). Cell 172: 318-‐330.

- Brain tumor cells interconnect to a functional and resistant network Osswald M, et al. (2015).. Nature 528: 93-‐98.

- Transmembrane proteoglycans control stretch-‐activated channels to set cytosolic calcium levels Gopal S, et al. (2015).. J Cell Biol 210:1199-‐211


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Haruhiko Bito, PhD (Department of Neurochemistry, University of Tokyo)

Haruhiko Bito graduated from the University of Tokyo with an MD in 1990 and a PhD in Biochemistry in 1993. After a postdoctoral training at Stanford University as an HFSP long-‐term fellow with Richard W Tsien, he became an Assistant Professor in 1997, and then after a Senior Lecturer in Pharmacology at Kyoto University in 1998, before moving to head the Department of Neurochemistry at the University of Tokyo in 2003 as an Associate Professor. Dr Bito is a Professor and Chair of Neurochemistry at the University of Tokyo Graduate School of Medicine since 2013. He has deciphered many novel functions of a family of molecules called Ca2+-‐

calmodulin kinases, and elucidated the bidirectional neuronal signaling between the synapses and the nucleus, both of which are essential for establishing long-‐term memory. Dr Bito is also known for inventing powerful molecular tools (E-‐SARE, R-‐CaMP2, and XCaMPs) that help control and measure neuronal ensemble activity critical for cognition. Selected Publications:

- Critical Neurodevelopmental Role for L-‐Type Voltage-‐Gated Calcium Channels in Neurite Extension and Radial Migration Kamijo S, et al. (2018) Neurosci. 38: 5551-‐5566.

- Rational design of a high-‐affinity, fast, red calcium indicator R-‐CaMP2. Inoue M, et al. (2015) Nature Methods, 12: 64-‐70.

- Region-‐specific activation of CRTC1-‐CREB signaling mediates long-‐term fear memory. Nonaka M, (2014). Neuron, 84: 92-‐106, 2014.

- Functional labeling of neurons and their projections using the synthetic activity-‐dependent promoter E-‐SARE. Kawashima T, et al. (2013) Nature Methods. 10: 889-‐895.

Mark Scnitzer, PhD (Stanford University, USA) Mark J. Schnitzer is an HHMI Investigator and a faculty member in Stanford’s Departments of Biology & Applied Physics. Starting with his early work at Bell Laboratories, his research has focused on the innovation and application of novel optical imaging technologies for brain science and understanding how large neuronal ensembles control animal behavior. The Schnitzer lab has innovated several technologies that are now commercially available, including tiny fluorescence microscopes small enough to be mounted on the head of a freely moving mouse and microendoscopes capable of monitoring single neuronal motor units in human patients

(Neuron, 2015). The former technology won The Scientist’s Top Innovation of 2013, was a finalist for the 2013 Israel Brain Prize, was Nature Method's "2018 Method of the Year", is now available from Inscopix Inc., and is presently used by >500 neuroscience labs worldwide in the USA, Asia and Europe. Schnitzer's work on brain imaging was recognized by the 2010 Young Investigator Award from the Biophysical Society. He was also a member of the NIH BRAIN Initiative Advisory Committee that wrote the BRAIN 2025 report. His lab is using its optical inventions extensively to study neural


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circuits in behaving mice and flies. Schnitzer's biological interests center on understanding the large-‐scale circuit dynamics underlying cognition, long-‐term memory and brain disease (e.g. Nat. Neurosci. 2013; Neuron 2015; Nature 2015; Nature 2017a; Nature 2017b; Nature 2017c; Nature 2018, Science 2019), including across multiple brain areas (Nat. Neurosci. 2014a, Cell 2019). Recently, Schnitzer has been investigating different classes of optical voltage-‐indicators (Nature Comm. 2014; Nat.Neurosci.2014b; Science 2015; Cell 2016, Nature Methods 2018). Schnitzer's trainees have had noteworthy successes and fourteen now are principal investigators. Selected Publications:

-‐ An amygdalar neural ensemble that encodes the unpleasantness of pain. Corder G, et al. (2019) Science. 363(6424):276-‐281.

-‐ Fast, in vivo voltage imaging using a red fluorescent indicator. Kannan M, et al. (2018) Nat Methods. 15(12):1108-‐1116.

-‐ Long-‐Term Consolidation of Ensemble Neural Plasticity Patterns in Hippocampal Area CA1. Attardo A, et al. (2018) Cell Rep. 25(3):640-‐650.e2.

-‐ Three-‐photon imaging of mouse brain structure and function through the intact skull. Wang T, et al. (2018) Nat Methods. 15(10):789-‐792.

Karl Deisseroth, PhD ( Stanford University, USA) Karl received his bachelor's degree from Harvard in 1992, his PhD from Stanford in 1998, and his MD from Stanford in 2000. He completed postdoctoral training, medical internship, and adult psychiatry residency at Stanford, and he was board-‐certified by the American Board of Psychiatry and Neurology in 2006. He tries to find spare time for flyfishing. Selected Publications:

-‐ Crystal structure of the natural anion-‐conducting channelrhodopsin GtACR1. Kim YS, et al. (2018) Nature.

-‐ Structural mechanisms of selectivity and gating in anion channelrhodopsins. Kato HE, et al.(2018) Nature.

-‐ Three-‐dimensional intact-‐tissue sequencing of single-‐cell transcriptional states. Wang Xiao, et al. (2018) Science.

-‐ 5-‐HT release in nucleus accumbens rescues social deficits in mouse autism model. Walsh JJ, et al.(2018) Nature.

Peter Hegemann, PhD (Humboldt University of Berlin, Germany) Peter Hegemann is head of the working group for experimental biophysics and Hertie Senior Professor of Neuroscience at the Humboldt University of Berlin. The world’s leading expert in photobiology is one of the founding fathers of optogenetics, which combines the methods of optics and genetics to create a form of non-‐invasive stimulation of neurons. His research with photoreceptors of algae has led to the discovery of light-‐sensitive ion compositions in cells. The protein involved (“channelrhodopsin-‐2”) enables a precise control of genetically modified cells through light pulses, which leads to a new possibility to treat neuronal illnesses. Peter Hegemann has been awarded the Gairdner Prize, the Gottfried Wilhelm Leibniz Prize of the German Research Foundation (DFG), the Grete Lundbeck European Brain Research Prize, the Harvey


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Prize and the Otto Warburg Medal. He is a member of the National Academy of Science and Engineering (acatech), the Berlin-‐Brandenburg Academy of Sciences and Humanities (BBAW), the European Molecular Biology Organization and the German National Academy of Sciences (Leopoldina). Selected Publications:

-‐ Tracking pore hydration in channelrhodopsin by site-‐directed infrared-‐active azido probes. Krause BS, et al. (2019) Biochemistry. Jan 31.

-‐ Crystal structure of the red light-‐activated channelrhodopsin Chrimson. Oda K, et al. (2018) Nat Commun. Sep 26;9(1):3949.

-‐ Electrical properties, substrate specificity and optogenetic potential of the engineered light-‐driven sodium pump eKR2. Grimm C, et al. (2018) Sci Rep. Jun 18;8(1):9316.

-‐ Rhodopsin-‐cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain. Scheib U, et al. (2018) Nat Commun. May 24;9(1):2046.

Stephane Dieudonne, PhD, (IBENS, Ecole Normale Supérieure, Paris, France) Stéphane Dieudonné is a cellular and systems neurobiologist with expertise in both electrophysiology and imaging of neuronal activity. During his PhD thesis under the supervision of Philippe Ascher (Paris, France), he studied glycinergic transmission and produced the first patch-‐clamp recordings of Golgi interneurons and Lugaro interneurons in the cerebellum. Following a short postdoc in the laboratory of K. Delaney (SFU, Vancouver, Canada), where he learned calcium imaging, he was recruited as a permanent researcher by INSERM in 2001. Anticipating the neurophotonics revolution, Stéphane Dieudonné has been an important contributor to the development of Random-‐Access Multiphoton microscopy, as a strategy for fast optical

recording and actuation of neuronal activity. He is involved in several international training courses in optics for the neurosciences and acts as scientific director of the imaging facility at the Biology Institute of the Ecole Normale Supérieure (IBENS). Since 2005, he has been heading a research team at IBENS, investigating the function of inhibitory neurons in neuronal homeostasis and computation. The group has identified functional organizing principles of mixed GABA/glycine inhibitory transmission at the molecular and microcircuit levels and described long-‐range inhibitory pathways involved in motor control. The team is now combining molecular and cellular expertise in optogenetics with the implementation of Random-‐Access imaging and actuation technology in the behaving animal to answer fundamental questions on the role of cerebellar microcircuits in motor learning and motor control. Selected publications:

-‐ Optogenetic stimulation of complex spatio-‐temporal activity patterns by acousto-‐optic light steering probes cerebellar granular layer integrative properties. Hernandez O, et al. (2018) Sci Rep. Sep13;8(1):13768.

-‐ Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit. Zampini V, et al. (2016) Elife. 2016 Sep 19;5. pii: e15872.

-‐ A subcortical inhibitory signal for behavioral arrest in the thalamus. Giber K, et al. (2015) Nat Neurosci. 18:562-‐8.


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-‐ Activity-‐dependent gating of calcium spikes by A-‐type K+ channels controls climbing fiber signaling in Purkinje cell dendrites. Otsu Y, et al. (2014) Neuron. 84 : 137-‐51.

Thomas Oertner, PhD (Hamburg Eppendorf University, Germany) Thomas Oertner studied Biology at the University of Freiburg in Germany, spending a year abroad (1993) in Scotland at the University of Edinburgh. For his Diploma and PhD thesis, he joined Axel Borst’s group at the Friedrich Miescher Laboratory of the Max-‐Planck-‐Society in Tübingen in 1996, working on calcium signaling in the visual system of the blowfly. From 2000 to 2003, he studied glutamate release and calcium signals in dendritic spines with Karel Svoboda in Cold Spring Harbor, NY. In 2003, Thomas Oertner started his own research group at the Friedrich Miescher Institute in Basel, Switzerland, part of the Novartis Research Foundation.

Since 2011, he is Professor for Neuroscience at the University of Hamburg and Director of the Institute for Synaptic Plasticity at the ZMNH. For many years, Thomas Oertner has been on the faculty of summer courses in Woods Hole, Cold Spring Harbor and Lausanne, teaching two-‐photon microscopy and optogenetics. His research is centered on the synaptic mechanisms of learning and memory, connecting the activity and plasticity of identified synapses to their long-‐term stability. The primary model system is the rodent hippocampus; experiments typically involve a combination of two-‐photon microscopy, optogenetic excitation and electrophysiological recordings. To investigate the links between synaptic plasticity, spatial learning and memory recall, he studies how precisely timed optogenetic inhibition interferes with mouse behavior in spatial memory tasks. Selected publications:

-‐ The fate of hippocampal synapses depends on the sequence of plasticity-‐inducing events. Wiegert JS, et al. (2018) eLife 2018;7:e39151.

-‐ Ultrafast glutamate sensors resolve high-‐frequency release at Schaffer collateral synapses. Helassa N, et al. (2018) PNAS 115:5594-‐9.

-‐ Conversion of channelrhodopsin into a light-‐gated chloride channel. Wietek J, et al. (2014) Science 344: 409-‐12.

-‐ Long-‐term depression triggers the selective elimination of weakly integrated synapses. Wiegert JS, Oertner TG (2013) PNAS 110: E4510-‐9.

Valentina Emiliani, PhD (Paris Descartes, France) Valentina Emiliani after having obtained her PhD in Physics in Rome, joined in 1998 the Max Born Institute (Berlin), to investigate carrier transport in quantum wire by low temperature scanning near field optical microscopy (SNOM). In 2002 she was offered a position at the European Laboratory for Nonlinear Spectroscopy (LENS) to lead a research group focused on the investigation of light propagation in disordered structure by SNOM. In 2002 she moved to Paris at the Institute Jacques Monod to start a

new interdisciplinar activity at the interface between physics and biology. Her interest was to study the role of mechanical forces on the establishment of cell polarity by optical tweezers. In 2004 she


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was recruited at the CNRS, to begin her project on optical control of neuronal activities with light. This project was awarded in 2005 by a European Young Investigator grant. In 2005 she moved at the university Paris Descartes where she formed the “Wave front engineering microscopy” group. The team has pioneered the use of wave-‐front engineering for neuroscience. In particular, they demonstrated a number of new techniques for efficient photoactivation of caged compounds and optogenetics molecules, techniques based on computer generated holography, generalized phase contrast and temporal focusing1–7. She became research director in 2011 and since 2014, she has been appointed Director of the

Neurophotonics laboratory. On April 2018, she moved the wave front engineering microscopy group at the Vision Insitut in Paris where she has also taken the head of the photonics department. In 2015 she has been awarded with the Prix “Coups d’élan pour la recherche française” from the Bettencourt-‐Shueller foundation and in 2017 she has been awarded with the Axa chair “Investigation of visual circuits by optical wave front shaping “. Selected Publications:

-‐ Thermal model of temperature rise under in vitro and in vivo two-‐photon optogenetics brain stimulation. Picot, A. et al. (2018) Cell Rep. 24, 1243–1253.

-‐ Temporally precise single-‐cell-‐resolution optogenetics. Shemesh, O. A. et al. (2017) Nat. Neurosci. 20, 1796–1806.

-‐ Three-‐dimensional spatiotemporal focusing of holographic patterns. Hernandez, O. et al. (2016) Nat. Commun. 7, 11928.

-‐ Spatially selective holographic photoactivation and functional fluorescence imaging in freely behaving mice with a fiberscope. Szabo, V., et al. (2014) Neuron 84, 1157–1169.

Tom Kash, PhD (University of North Carolina , USA) My broad scientific goal is to understand how modulation of discrete neuronal circuits can shape behavior and to deconstruct the molecular mechanisms that underlie this modulation. Research in my lab is focused on understanding how stress and alcohol abuse can alter neuronal function in brain regions that regulate emotional behavior. These topics are fascinating from a basic science standpoint, but also absolutely critical from the public health standpoint, as these disorders exert a tremendous economic impact on our society. These investigations are performed using a multidisciplinary approach, ranging from behavioral analysis to detailed mechanistic signaling analysis in individual neurons. This integrative approach has been exciting and has allowed me to move my science beyond correlation to explore causative relationships. I have multiple active projects and grants related to discovering different aspects of stress and alcohol induced behavioral pathologies. Selected publications:

-‐ Fear extinction requires infralimbic cortex projections to the basolateral amygdala. Bloodgood DW, et al (2018). Transl Psychiatry. Mar 6;8(1):60.

-‐ The bed nucleus of the stria terminalis in drug-‐associated behavior and affect: A circuit-‐based perspective. Vranjkovic O, et al. (2017) Neuropharmacology Aug 1.

-‐ Chronic EtOH effects on putative measures of compulsive behavior in mice. Radke AK, et al (2017). Addict Biol. Mar;22(2):423-‐434.


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-‐ Acute engagement of Gq-‐mediated signaling in the bed nucleus of the stria terminalis induces anxiety-‐like behavior. Mazzone CM, et al. (2016) Mol Psychiatry. Dec 13.

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