NIN News. N I N C e n t e n n i a l. June Netherlands Institute for Neuroscience

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1 NIN News June 2009 Netherlands Institute for Neuroscience N I N C e n t e n n i a l A hundred? Indeed it feels like yesterday that I gave a similar speech at the opening of the NIN. As a theoretical physicist I can tell you that Einstein s theory of relativity allows for this (...), as Robbert Dijkgraaf, president of our proud parent the KNAW said in his opening speech of the symposium on 12 June. Perhaps in retrospect, the early visions of those days were a bit naive. It s very difficult to think of DNA or fmri in Just as one will probably wonder in the year 2109 how we could possibly try to understand the brain without a quantum interference neuron spectrometer. One thing is clear: understanding the brain and cognition in all its complexities will be a crucial central theme, if not the central theme in science of the coming century. This was true in 1909 but I think it s even more true in In fact we just celebrated the one hundredth birthday of the Central Institute for Brain Research. It has recently evolved into NIN, together with the Netherlands Ophthalmic Research Institute, as was pointed out by our director Pieter Roelfsema in his introductory historical overview. extensively on the front page of the Algemeen Handelsblad of 8 June From the start, the institute was internationally oriented and it hosted many foreign guest researchers, with Kappers himself spending time as a visiting professor at many foreign universities, such as Beijing Union Medical College (1923) and Beirut (1928). His life s work has been taken down in his twovolume book, The comparative anatomy of the nervous system of vertebrates, including man (MacMillan 1936, co-authors Crosby and Huber), which is still in use (...). Professor Ariëns Kappers received many prizes and was awarded honorary doctorates in Glasgow, Dublin, Chicago and Yale. He died in 1946, at the age of 68. His memoirs were not published until (C.U. Ariëns Kappers, Reiziger in Breinen, ISBN ) Organizers Michel Hofman and Dick Swaab had invited five renowned lecturers. Among them Frans de Waal, who would deliver the 19 th C.U. Ariëns Kappers lecture later that day. He received the award from Dick Swaab: We honour today two exceptional scientists. C.U. Ariëns Kappers, who became the first director of our institute one hundred years ago and whose main research topic was comparative neurology and the evolution of the brain, and the primatologist Dr. Frans de Waal, who has contributed so much to our knowledge of the evolution of behaviour(...). The Central Institute for Brain Research was the first institute established in the Netherlands with the express purpose of carrying out pure scientific research, as is stated, not without pride, in speeches held during the opening, which was reported

2 Frans de Waal is the author of numerous books, including Chimpanzee politics and Our Inner Ape, Dick Swaab continued. His research into the innate capacity for empathy among primates has led the Waal to the conclusion that humans are simply different types of apes and that there are little essential differences between the species. As de Waal himself said: I have argued that many of what philosophers called moral sentiments can be seen in other species. In chimpanzees and other animals you see examples of sympathy, empathy, reciprocicity and a willingness to follow social rules. And to endow animals with human emotions had long been a scientific taboo, but if we do not, we risk missing something fundamental about animals and us. (...) In 2007, de Waal was named one of Time Magazine s one hundred most influential people. He has been elected to the National Academy of Sciences of the USA, the American Academy of Sciences and to the Royal Netherlands Academy of Arts and Sciences (KNAW). It is important to note that the experiments that according to the standards of de Waal one is allowed to do with hominids, are of a non-invasive nature, the type of experiments one can do with human volunteers. This principle has certainly contributed to the rapid translation of his experiments for human neuroscience. It s a great honour for me to offer the C.U. Ariëns Kappers medal this year to professor Frans de Waal for his extraordinary contribution to the fields of primate behaviour and social psychology, that has given such an original and deep insight into our own behaviours and motivations. C.U. Ariëns Kappers Award Laureates Pasco Rakic New Haven, USA, 1987 Anders Björklund Lund, SWE, 1988 Mortimer Mishkin Bethesda, USA, 1989 Robert Y. Moore New York, USA, 1991 Dale Purves Durham, USA, 1993 Joseph Takahashi Evanston, USA, 1995 Patricia S. Goldman Rakic New Haven, USA, 1996 Dean H. Hamer Bethesda, USA, 1999 Gerald M. Edelman San Diego, USA, 1999 Vilayanur S. Ramachandran San Diego, USA, 1999 Steven P.R. Rose Milton Keynes, GBR, 1999 Michael S. Gazzaniga Hanover, USA, 1999 Antonio R. Damasio Iowa City, USA, 1999 Rudolf Nieuwenhuys Amsterdam, NLD, 2000 Mark H. Tuszynski San Diego, USA, 2001 Dennis D.M. O Leary La Jolla, USA, 2003 Clifford B.Saper Boston, USA, 2005 James Fawcett Cambridge, GBR, 2008 Frans B.M. de Waal Atlanta, USA, 2009 Organizer Michel Hofman had started the day by introducing the lecturers and welcoming the guests. Among them were Robbert Dijkgraaf, Theo Mulder and Robert Kaptein from KNAW, Nico Frijda, Jan van Hooff, Peter Hagoort, Henk Groenewegen, Arjen Brussaard, Marian Joëls, Fernando Lopes da Silva, Ton Lohman, Albert Verveen, Ron de Kloet, Peter Burbach, Walter van Emde Boas, Netty van Lookeren Campagne, Pieter and Erik Ariëns Kappers, and Rudolf Nieuwenhuys, the latter also having attended the 50 th birthday in 1959 as a PhD student. J.H. Luo and Aimin Bao came over from Hang Zhou, China. Simon E. Fisher from Oxford, UK, a Royal Society research fellow, started the morning session with a beautiful lecture about Molecular windows into speech and language. Fisher is a pioneer in neurogenetics, having conducted the first large-scale scans across all chromosomes of the genome for developmental dyslexia, language impairment and ADHD. He showed us that a mutation in a regulatory gene, called FOXP2, causes an inherited speech and language disorder. His research is the first to show that a gene can be clearly linked to speech and language skills. Ivanca Savic from Stockholm, Sweden, conducts research on the neurobiology of the human limbic system including amygdala and its projections with a special interest in sex differences in these systems. Another research line concerns the cerebral processing of odorous stimuli in humans in relation to sexual orientation. She lectured on Cerebral activation and connectivity in relation to sex and sexual orientation.

3 After Chris de Zeeuw, our project director, had thanked the speakers and organizers, we all embarked on a canal cruise, heading for the party at the Rode Hoed, where we had an excellent dinner accompanied by gypsy music. When the DJ started to take care of the digestion of this fruitful day, we were happy to see that some of our guest speakers took the floor to show skills that were not restricted to the mind. N I N K E Y P U B L I C A T I O N S The afternoon saw a very lively presentation by Alcino J. Silva, professor at UCLA, in which he unraveled molecular and cellular mechanisms of memory allocation in neurocircuits seemingly before our eyes. Dr. Silva and his group study the biology of learning and memory with a focus on hippocampal/prefrontal memory mechanisms. He studies molecular, cellular and circuit processes that underlie the encoding, storage and recall of information in the brain. Dean Falk from Florida State University, Tallahassee, USA is well known for her work on the evolution of the brain and cognition in higher primates, including humans, and the origin of language. She is the author of Braindance: New Discoveries About Human Origins and Brain Evolution (1992) and Primate Diversity (2000). Falk linked the early days of our institute to important paleontological findings of the time before she gave her lecture on Missing links, human brain evolution and paleopolitics. Prosocial primates: empathy, fairness and cooperation was the title of Frans de Waal s lecture. If you look at the United States: we have a banking crisis, a financial crisis and actually Holland had a major financial crisis also. People are very upset about the big bonuses of the bankers. It is very interesting for me because at the end I will say a few things about fairness and how my monkeys react to unfair situations, which is exactly what s happening in the US today. So greed is out, everywhere, empathy and fairness are in. De Waal showed us wonderful movies of monkeys, dogs and elephants, that were very moving indeed, demonstrating more empathy, fairness and cooperation than what we are used to. He concluded: Empathy and imitation are ancient capacities; primates know cooperation and reciprocity, and cooperation fosters sharing and concern for welfare of others and fairness. Allikmets, R., Bergen, A.A.B., Dean, M., Guymer, R.H., Hageman, G.S., Klaver, C.C., Stefansson, K., Weber, B.H. and the international Age-related Macular Degeneration Genetics Consortium. Geographic atrophy in age-related macular degeneration and TLR3. New Engl J Med. 360 (2009) Klieverik, L.P., Janssen, S.F., Van Riel, A., Foppen, E., Bisschop, P.H., Serlie, M.J., Boelen, A., Ackermans, M.T., Sauerwein, H.P., Fliers, E., and Kalsbeek, A. Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. PNAS 106 (2009) Koten, J.W., Wood, G., Hagoort, P., Goebel, R., Propping, P., Willmes, K., and Boomsma, D.I. Genetic contribution to variation in cognitive function: An fmri study in twins. Science 323 (2009) Stöhr, H., Heisig, J.B., Benz, P.M., Schöberl, S., Milenkovic, V.M., Strauss, O., Aartsen, W.M., Wijnholds, J., Weber, B.H., and Schulz, H.L. TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals. Journal of Neuroscience 29 (2009) Van Leeuwen, M., Fahrenfort, I., Sjoerdsma, T., Numan, R., and Kamermans, M. Lateral gain control in the outer retina leads to potentiation of center responses of retinal neurons. Journal of Neuroscience 29 (2009) Van Woerden, G.M., Hoebeek, F.E., Gao, Z., Nagaraja, R.Y., Hoogenraad, C.C., Kushner, S.A., Hansel, C., De Zeeuw, C.I., and Elgersma, Y. βcamkii controls the direction of plasticity at parallel fiber-purkinje cell synapses. Nature Neuroscience 12 (2009) A N N O U N C E M E N T S Amsterdam International Medical Summer School, 5-31 July 2009 Exploring the brain from function to dysfunction How do we see, do neurons regenerate, what happens when we electrically stimulate the brain, and why do we need a hypothalamus? This Summer School will focus on exciting recent progress in medicine and neurosciences. The program will include lectures on four major topics stretching from basal neuroscience to practical medicine, including visual perception, neurodegeneration, neuromodulation and neuro-endocrinology. Programme committee: P.A.J.P. Denys, E. Fliers, P.R. Roelfsema, D.F.Swaab, and G.E.A. ten Have. exploring-the-brain-from-function-to-dysfunction-medic-1/

4 r e s e a r c h i n f o c u s The Synapse and Network Development group started at the NIN in April Christian Lohmann, the team leader, had previously worked in the department of Tobias Bonhoeffer at the Max Planck Institute of Neurobiology in Munich. Team members Friederike Siegel and Thomas Kleindienst came from Munich, too, where they had started their PhD projects, which they will now finish at the NIN. 0 sec 36 sec Recently we discovered a new mechanism of how dendrites select new synaptic partners, which we described in a Neuron paper last year: Small dendritic processes establish contact with axons and within a minute after a contact is formed they start generating calcium signals. If the contacted axon is appropriate, the calcium activity in the dendrite will be high and the contact will become stabilized. It can then turn into a functional synapse. If the axon is not an appropriate synaptic partner, however, little calcium activity will be generated and eventually the dendrite retracts, thereby breaking up the contact and the search for synaptic partners continues. A c a d e m y C o l l o q u i u m 3 µm Figure 1. Left: live dendrites (orange) and axons (green) labeled in a hippocampal slice. Above: a dendrite contacts an axon. We investigate how neurons establish specific functional contacts with each other during the development of the brain. We use various types of microscopes, such as wide-field, confocal and two-photon, to directly watch neurons contacting each other (Fig. 1) and selecting appropriate synaptic partners. Furthermore, we visualize different forms of signaling in developing neurons, such as synaptic activity and neurotrophin triggered signaling, by imaging changes in the intracellular calcium concentration. This can even be done in live animals at single synapse resolution (Fig. 2). Nutrition, Metabolism and the Brain The main topic that we wished to emphasize during this Academy Colloquium is: The emerging role of the hypothalamus as a crucial link between sensing nutrients and the control of insulin sensitivity, glucose uptake, and glucose production. The Academy Colloquium started of on Monday 11 May with a Masterclass at the Netherlands Institute for Neuroscience. The Masterclass was attended by ca 35 PhD students and consisted of 4 presentations in the morning by the masters (i.e., a selection of invited speakers at the colloquium) and 10 presentations by PhD students in the afternoon. The students all acknowledged the lively discussions and the devoted attention of the masters. The colloquium itself (12-14 May) took place in the Trippenhuis in the centre of Amsterdam and was opened by Robbert Dijkgraaf (President KNAW). On the three days, 17 presentations were given by invited speakers, 13 presentations by authors of selected abstracts and 15 poster presentations. In total about 100 clinicians and basic scientists from all over the world attended the colloquium. The two responses pasted below very well represent the many positive reactions the organizing committee received during and after the meeting: I wanted to thank you again for the meeting. It was really great and Thanks very much for inviting me to the meeting and all your hospitality while I was there. It was an excellent meeting. Organizing committee: Dries Kalsbeek, Eric Fliers, Gertjan van Dijk, Hanno Pijl, Susanne lafleur, Etienne Challet and Czaba Nyakas. Figure 2. Left: In vivo image of dendrites filled with a calcium indicator. Right: Synaptic calcium transient recorded in a dendritic spine in the visual cortex of a young mouse.

5 D I S S E R T A T I O N S 12 March 2009 Nathalie Koning Imbalanced immunity in multiple sclerosis. Dick Swaab and René Van Lier (AMC), supervisors. Inge Huitinga and Robert Hoek, co-supervisors. Nathalie Koning started in 2004 with her PhD work at the NIN in the Neuroimmunology Research group. Her research focused on the immune suppressive mechanisms that control macrophages and microglia in multiple sclerosis. She was funded by the Dutch MS Research Foundation. Since October 2008, she works as a post-doc in the group of Van Kooyk, Department of Molecular Cell Biology and Immunology, VUmc. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Crucial for the development of MS lesions are highly activated macrophages and microglia. The disproportional activation of these cells reflects an imbalanced immune regulation in the CNS, but it is unknown whether this is due to enhanced activating signals, decreased inhibition or a combination of both. Importantly, in the normal immuneprivileged CNS, powerful systems such as CD200-CD200R and CD47-SIRPα interaction continuously suppress local immune activities. We have shown that expression of CD200 and CD47, but not of their receptors on macrophages/microglia, was diminished in MS lesions. These data indicate that decreased immune inhibition may contribute to a disturbed equilibrium in macrophage and microglia activation in MS. Furthermore, we have shown the cellular localization of CD200 and CD200R in the CNS, and we addressed the regulation of CD200R on macrophages and microglia. We suggest that targeting macrophages/microglia, for example by enhancing CD200R signaling, could have an important therapeutic potential and would be a new, unexplored field in the treatment of MS. 22 April 2009 Sridhara Chakravarthy Regulation of spine maintenance in the adult mouse visual cortex by TrkB signaling. Matthijs Verhage (VU), supervisor. Christiaan Levelt, co-supervisor. Sridhara Chakravarthy started in 2001 with his PhD work at the NIN in the Molecular Visual Plasticity group. He worked on the role of TrkB signaling in adult visual cortex. Since 2008 he works as a post-doc in the group of Cohen-Cory, Department of Neurobiology and Behavior, University of California, Irvine, USA. The role of TrkB/BDNF-signaling in the developing and immature brain is multifaceted. However, it has been difficult to study the effects of BDNF in the intact adult brain, without influencing the development of the brain. This thesis aims at elucidating the role of TrkB signaling in adult cortical plasticity to answer some of the following questions. What are the structural and functional effects of inhibiting TrkB signaling in the adult cortex? Are these effects different in a similar cell type from another brain area? Can the pre- and post-synaptic effects of TrkB signaling be discerned? Does TrkB signaling act as a competitive substrate for cortical plasticity? What are the mechanisms that bring about these effects? By generating transgenic mice expressing a dominant negative TrkB-EGFP in isolated excitatory neurons of the adult forebrain, we show that postsynaptic TrkB signaling is crucial for the maintenance of synaptic strength in the mature visual cortex but not in the hippocampus. However, spine maintenance is not compromised in transgenic mice that express TrkB-EGFP in a majority of excitatory neurons of the adult visual cortex, although they receive reduced inhibitory input. We hypothesize that synaptic maintenance by postsynaptic TrkB signaling is a competitive process controlled by the inhibitory system which, in turn, is triggered by population activity.

6 C A L E N D A R 13 July 2009 Lecture by Jonathan Victor (Weil Cornell Med Coll., NY, USA) Information-theoretic analysis of neural data: why it is challenging, and what can be learned Faculty building Erasmus MC Rotterdam, Room Ae July 1 August 2009 CogSci 2009 Vrije Universiteit Plenary speakers: Susan Carey, Nicola Clayton, Stanislas Dehaene, Randall O Reilly, Joshua Tenenbaum August 2009, 14:00 h Swammerdam Lecture by Jeffrey Dalley (University of Cambridge, Cambridge,UK). The behavioural neuroscience of impulsivity and compulsivity: cross-species analysis August 1 September 2009 EMBO-Meeting Amsterdam 2009, RAI Amsterdam. Organizers: Hans Clevers and Stephan West (UK) 11 September 2009 Swammerdam Lecture by David Ginty (Johns Hopkins University School of Medicine, Baltimore, USA) Growth and survival signals controlling development of the peripheral nervous system NIN colloquium room. Host: Joost Verhaagen September 2009, 10:00 h Lars P. Klieverik will defend his thesis Thyroid hormone, Metabolism and the Brain. Promotores: E. Fliers en H.P. Sauwerwein. Copromotores: A. Kalsbeek en M.T. Ackermans UvA, Agnietenkapel. 17 September 2009, 13:00 h Xtrack Symposium: Buy or Sell!? The neurobiology behind decisions Uithof, Utrecht 21 September 2009, 20:00 h Lecture by Dick Swaab: De evolutie van onze hersenen Diligentia, Den Haag. 7 October 2009 Swammerdam Lecture by David McCormick (Department of Neurobiology, Yale University, New Haven, USA) Cortical network dynamics NIN colloquium room. Host: Christiaan Levelt October 2009 European Retina Meeting 2009, Oldenburg, Germany. Heads of the Scientific Organizing Committee: Reto Weiler and Maarten Kamermans October 2009 Fifth Cognition Autumn School Doorwerth, Netherlands From stimulus to understanding in perception and language olthoff@fsw.leidenuniv.nl 30 October 2009, 15:00 h Swammerdam Lecture by Carl Petersen (Ecole Polytechnique Fédérale de Lausanne, Switserland). Synaptic mechanisms of sensory perception SILS - UvA 2 November 2009 Lecture by Kristen Verhey (Univ Michigan, USA) Road signs for kinesin motor transport Faculty building Erasmus MC Rotterdam, Room Ae November 2009 Swammerdam Lecture by Gilles Laurent (Division of Biology, Caltech, Pasadena, USA) Dynamics and coding in an olfactory circuit SILS - UvA 19 November 2009 Swammerdam Lecture by Tim Tully (Dart Neuroscience LLC, San Diego, CA, USA) Enhancing Memory Woudschoten Conference center, Zeist. Host: Daniëlle van Versendaal (NIN) 7 December 2009 Lecture by Fritjof Helmchen (Univ. Zürich, Switzerland) Neuronal population responses revealed by in vivo two-photon microscopy Faculty building Erasmus MC Rotterdam, Room Ae 406. NIN News edited by Jenneke Kruisbrink Henk Stoffels Chris De Zeeuw Contact: news@nin.knaw.nl Netherlands Institute for Neuroscience Meibergdreef BA Amsterdam The Netherlands