Annual Report 2007 Biology ofMemory Centre for the and Systems Kavli Institute for Group members 27 Mars 2008 (Photo: Gorm Kallestad/Scanpix)

Group leaders May-Britt Moser, Menno Witter and (Photo: Raymond Skjerpeng/KI-CBM)

Front cover: Entorhinal innervation of parvalbumine positive neurons in the hippocampus. (Photo: Floris G. Wouterlood and Amber Boekel).

 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Table of Contents

Recognition, expansion and change 4

NTNU KI-CBM begins its second period Kavli Institute for Systems Neuroscience as a Norwegian Centre of Excellence 6 and Centre for the Biology of Memory Centre of Excellence Bettencourt prize finances new research 7 Medical-Technical Research Centre NO-7489 KI-CBM becomes first Nordic Kavli Institute 8 Menno Witter becomes new member of KI-CBM 10 Telephone: + 47 73 59 82 42 Telefax: + 47 73 59 27 90 A confirmation of excellence 12 E-mail: [email protected] Honours and prizes to young CBM and KI researchers 14

Annual accounts 15

Who’s Who 16

Publications 18

Annual Report published by the Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory.

Editor: Director Edvard Moser

Text: Bjarne Røsjø Media, N1253 Hege Tunstad, KI-CBM

Translation: Nancy Bazilchuk

Photo: Haagen Waade, KI-CBM Gorm Kallestad, Scanpix Geir Mogen, NTNU-Info Mentz Indergaard, NTNU-Info

Layout: Haagen Waade, KI-CBM

Print: Tapir Uttrykk NO-7005 Trondheim

Brainslices stained with cresylviolet (Photo: Gorm Kallestad/Scanpix)

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory  Recognition, expansion and change

In the next five years, we want to use the discoveries we have made to understand complex functions in the whole brain, say CBM and Kavli Institute directors Edvard and May-Britt Moser. (Photo: Geir Mogen/NTNU Info)

“2007 has been marked by recognition, “It’s also been important for us that the start-up funding from the European Re- expansion and change. The most important permanent scientific staff expanded in 2007, search Centre (ERC), as a result of Stefan event is clearly that the centre became the with the hiring of Professor Menno Witter, Leutgeb’s project application. It’s also that, 15th Kavli Institute in the world, which has who has now moved permanently to Trond- by hiring Witter, we’re laying the foundation involved quite a bit of recognition. Another heim. We have worked closely with him for to build bridges between basic research and important event has been the expansion of several years, but the move means that our clinical applied knowledge. Both Stefan and the permanent scientific staff, and we’ve also work will be that much more integrated. Menno represent knowledge and research gone through with some important realign- Witter is already working at full speed to that will contribute to making it easier in ments”, say May-Britt and Edvard Moser. build up a first-class and modern neuroana- the future to diagnose and treat diseases tomy laboratory,” adds director May-Britt such as Alzheimer’s, epilepsy and other ill- “The designation of the Kavli Institute for Moser. “The different groups at the centre nesses”, predicts Edvard Moser. Systems Neuroscience is the most promi- complement each other quite well, and now nent recognition we have received to date. we can work at a more in-depth level, and The Research Council’s Midterm Most of the Kavli Institutes are at presti- make important progress, while at the same Evaluation geous universities in the , such time we’ve expanded our scientific breadth, The midterm evaluation of the CBM as a as Harvard, Cambridge, Stanford, Yale, and are a stronger specialist group.” Norwegian Centre of Excellence gave the Caltech and MIT. We are the third Kavli centre top marks. “Now we’re halfway, and Institute in Europe, along with the Kavli A number of CBM’s researchers have been after five years it’s natural to think about Institute of Nanoscience at the Delft Uni- awarded important honours and awards the time that has passed, and the next five versity of Technology in the , in recent years, which is a source of pride years”, muses May-Britt Moser. “The first and the Kavli Institute for Cosmology at the and optimism. “It’s not just the enormous five years have been marked by the develop- ”, emphasizes CBM recognition that came from the centre being ment of our research group. We took as our director Edvard Moser. the only one in Norway that was awarded starting point the mechanisms for memory

 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory in the hippocampus. We began to realize signals that are produced and adapted by that will have more immediate applications. early on that a sense of location couldn’t just the brain. That means that spatial location is When basic research has clear conse- be the result of processes that take place in a good model for examining how the brain quences, it becomes our civic responsibility the hippocampus, so we therefore branched works”, explains Edvard Moser. to work with applications based on what we out into nearby cortical areas. We had to have found out. That is a central element expand into the surrounding cortex, and CBM researchers plan to use this model to in Stefan Leutgeb’s ERC proposal, which in the entorhinal cortex we found a central understand complicated thought processes looks at what goes wrong in the brain as a part of the brain’s spatial locater, namely a in the brain. “We’ll do that in two different result of Alzheimer’s disease, for example. person’s ability to figure out where he or she ways. The first is to take advantage of -in Additionally, Menno Witter is working with is located. That radically transformed our novations in gene technology, to get a better a research group at NTNU that wants to work. In the course of the first five years handle on causal processes. The centre has understand normal processes and pathologi- we’ve consequently made a discovery that now set up a virus laboratory where we will cal processes, such as are found in Alzheim- has not only transformed our own work, use harmless viruses to deliver genes to se- er’s disease and epilepsy”, she adds. but also the entire field. The understanding lected cell groups in the brain. By inserting of place representation in the brain today is genes into the target cells, these “delivery” “We would like to do our part to enhance quite different than it was just a few years viruses enable us to turn the cells on and the overall level of knowledge in the field, ago, because of the research that’s taken off as we like. By turning cells on and off, so we’re particularly pleased to be able to place here at the centre,” she emphasizes. we can find out which cell types have which arrange the Fridtjof Nansen conference on functions. Neural Networks and Behaviour in June Understanding the whole brain 2008. We’ll bring together some of the The centre’s goal has consequently expanded The other approach we’ll take is to use best researchers working at the nexus of and changed over the years. “With regards statistical analyses and modelling of activity their various disciplines and . to the next five years, we now want to use in a large network. The data we get from re- There’s been a great deal of interest in the the discoveries we’ve made to help in under- search are so wide-ranging and variable that conference already, and we have selected and standing the brain as a whole. To under- we will do well by running them through invited top-shelf researchers. These kinds stand the workings of the neural network a computer model to understand what is of conferences can contribute to lifting our in general, we’re using memory and spatial possible and what is not in specific neural overall understanding of the field. The best location as a starting point. The goal is that networks”, the researchers say. researchers from physiology, mathematics, in coming decades, we use this knowledge to physics, medicine and psychology whose dedicate ourselves to also understand other Expanded focus and social focus is on neural processes will be gathered cognitive functions, such as decision making responsibility in a place where they won’t only remember and social interactions, because these abili- CBM is a centre that is now pursuing a the conference because of its content, but ties probably have a great deal to do with variety of directions, in as much as its because the location is so unique that their the brain’s basic mechanisms. When all is various research efforts have grown. “Our memories of the experience won’t compete said and done we want to understand things fundamental focus is still on basic research. with other memories” says Edvard Moser, such as abstract thought and creativity”, We will use memory and sense of location with a twinkle in his eye. explain the two CBM directors. as a gateway to understand how the brain functions; that is the core of our work: we Not resting on their laurels Grid cells as a gateway want to understand the normal processes in “This discipline is developing so quickly “The reason that we now can do this is that the brain. Nevertheless, our focus has been now that if a researcher wants to be involved the mechanism for spatial location that we expanded to also include pathological condi- with the next advances and change the field found, the grid cells, are easy to locate in tions. Because the centre has more research- by contributing new knowledge, you have to the brain and have characteristics that are ers, it means that it’s possible for us to study do what you can to find ways to guarantee reliable and easy to measure. That means more of the brain, such as the structure, as is that you’re asking the right questions. We that we can use them as a gateway in under- being done by Menno Witter, and function also have to work on developing theories standing the general principles by which the and behaviour, as Stefan Leutgeb has begun and models that explain why things work neural network operates. Another impor- to do”, points out May-Britt Moser. together the way they do. We have gotten tant factor is that this is a phenomenon that a few laurels in 2007, but we’re not going is produced in the brain itself. In most of “Our research and findings have now come to rest on them. We don’t have time!” say our sensory systems, you’ll see changes in to the point where it’s appropriate to build Edvard and May-Britt Moser. the signals that come in from the outside, a bridge to clinical work. That won’t change and that are a reflection of the surroundings. our basic approach to understanding the These are adapted in the brain, while in grid normal nervous system, but at the same cells, it is first and foremost “homemade” time we’re doing this to generate knowledge

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory  KI-CBM begins its second period as a Norwegian Centre of Excellence

The Centre for the Biology of Memory (CBM) started its second period as a Nor- wegian Centre of Excellence (CoE) at the beginning of 2007, with financial support from the Research Council of Norway. The RCN contract was renewed after an inter- national evaluation stated that the centre had “by all standards been exceptionally suc- cessful during the first period of operation”.

The Research Council of Norway’s midway evaluation of the Norwegian Centres of Excellence, which was made public in finding that was not envisioned at the time October 2006, included much praise for of the application. CBM’s research and organization. CBM was one of 13 fields recognized as a Centre The scheme and the evaluation process of Excellence when the Research Council The Norwegian Centres of Excellence first established the programme in 2002. (CoE) scheme is designed to stimulate In the midway evaluation, CBM and eight Norwegian research groups to set up centres other centres were awarded top marks, or devoted to long-term basic research. The “exceptionally good”. With the completion of intention is to raise the quality of Norwe- the evaluation, CBM and other centres have gian research and bring more researchers now secured financing from the Research and research groups up to a high interna- Council of Norway until 2013. tional standard. The purpose of the midway evaluation was to assess the scientific quality The main conclusion from the international The midway evaluation’s main conclu- and performance of the individual centres evaluation of the CBM was that the centre has sion about CBM was that the centre has in absolute terms and relative to the centres’ had a major impact and has developed into a had a major impact and developed into a original research plans. major international centre for studies of the major international centre for studies of biology of memory. the biology of memory. “The centre has had The midway evaluation involved the prepa- (Pfoto: Gorm Kallestad/Scanpix) a remarkable series of high profile articles ration of extensive background material, an published in Nature, Science, Neuron and assessment of each centre by three inter- A privilege and an inspiration the Proceedings of the National Academy national experts, and an overall evaluation “It’s a privilege and an inspiration for of Science. The centre’s articles have had a made by an interdisciplinary, international NTNU’s Faculty of Medicine to be the very high impact, the quality is exceptionally evaluation committee chaired by Profes- host faculty for the Centre for the Biology high, and the quantity clearly satisfactory”, sor at the Nobel Institute for of Memory. The centre helps strengthen our the evaluation says. Neurophysiology, Karolinska Institutet, Faculty’s reputation, and puts our research Stockholm, Sweden. The overall impression activities on the world’s map”, says Stig A. The evaluation also observed that the was that the Norwegian CoEs have had a Slørdahl, Dean of the Faculty. centre’s international collaboration has very positive effect on Norway’s research been very important both with regard to environment in the disciplines for which “CBM’s naming as the Kavli Institute for methodology and concepts. “The structure CoEs have been established. Systems Neuroscience in August, along of the centre is somewhat unusual in that with the award of Stefan Leutgeb’s ERC except for the two directors, the remaining An efficient organization Starting Grant in December 2007, are principal investigators have been recruited The centre is run by the two directors in highlights that underscore the importance from Europe and North America. They what appears a very efficient way, according of having a Norwegian Centre of Excel- are international leaders in the different to the evaluation. “The Mosers and their col- lence at the faculty. As a research group at sub-disciplines within the centre’s field”, the leagues have established themselves as one the very forefront of international research, evaluation report states. of the leading research centres in memory CBM is both a model and a beachhead for research, which is one of the ‘hottest’ areas other groups in the Faculty. We have great The report also that stated that CBM had of brain research”, the evaluation says. The expectations for CBM in the years to come, worked according to its original plan, which report also stated that there is clearly a need and look forward to continuing our strong included milestones, but that the centre for more space for the centre and for ad- co-operative effort and to new scientific had also discovered grid cells – a major new ditional faculty. breakthroughs”, says Slørdahl.

 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Bettencourt prize finances new research

May-Britt and Edvard Moser received the Grid cells on Scholarpedia of the brain’s coordinate system for metric Liliane Bettencourt Life Sciences Award Edvard and May-Britt Moser were invited navigation. They have attracted attention in 2006 for their research and contribution in 2007 to write about grid cells for Schol- because the crystal-like structure underly- to the establishment of the Centre for the arpedia – the free scientific encyclopedia. ing their firing fields is not imported from Biology of Memory (CBM). In 2007, the Scholarpedia feels and looks like Wikipedia, the outside world, but created within the majority of the prize money was used to pay which is the free Internet encyclopedia that nervous system. Understanding the origin for the postdoctoral fellowship for Ro- anyone can edit. But one of the differences and properties of grid cells is an attractive samund Langston, who was recruited from between Wikipedia and Scholarpedia is that challenge for anyone wanting to know how the University of Edinburgh. each article in Scholarpedia is anonymously brain circuits operate. peer reviewed. The prestigious Bettencourt prize of EUR 250,000 is each year awarded to younger Both Scholarpedia and Wikipedia are European researchers with an international powered by the same program, called Me- reputation. The prize is intended to support diaWiki, and both allow visitors to review the work of a top-level European researcher and modify articles simply by clicking on the under the age of 45, along with his or her “edit this article” link. team, in the field of biology or medicine. However, Scholarpedia differs from Wiki- pedia in some very important ways: The Bettencourt prize money was divided in 2007 to allow 80 per cent to finance Ro- •Each article is written by an expert (invited samund Langston’s postdoctoral position. or elected by the public). Langston’s main research project concerns •Each article is anonymously peer reviewed whether the grid cell system is innate and to ensure accurate and reliable information. if the system is calibrated during growth. •Each article has a curator – typically its The Bettencourt money is also being used author – who is responsible for its content. to study temporal codes in grid cells. The •Any modification of the article needs to be results from this project have attracted a approved by the curator before it appears in great deal of international attention, and the final, approved version. will appear in Nature in 2008. Herein also lies the greatest differences between Scholarpedia and traditional print media: while the initial authorship and review processes are similar to a print journal, so that Scholarpedia articles can be cited, they are not frozen and outdated, but dynamic, subject to an ongoing process of improvement moderated by their curators.

In Scholarpedia, every article has a person who takes care of its content and whose reputation becomes associated with this content, the curator. The job of a curator is to moderate revisions of an article, accepting those that are relevant and rejecting those that are not. Scholarpedia curators are leading experts in their respective fields. A grid cell – according to May-Britt and Edvard Moser’s article in Scholarpedia – is a Grid cell recording in the entorhinal cortex: place-modulated neuron whose multiple fir- Top: Rosamund Langston training rat in open Rosamund Langston with one of her rats. field environment. ing locations define a periodic triangular ar- Rosamund is the postdoctoral fellow who was (Photo: Geir Mogen/NTNU Info) recruited from the University of Edinburgh with ray covering the entire available surface of an Bottom: Trajectory of the rat (black) with spike financing from the Bettencourt Prize. open two-dimensional environment. Grid locations superimposed (blue) recorded by (Photo: Gorm Kallestad/Scanpix) cells are thought to form an essential part Jonathan Whitlock/KI-CBM.

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory  KI-CBM becomes first Nordic Kavli Institute

The North American physicist, business- went to Canada with his engineering degree World-class research man and billionaire Fred Kavli designated and $300 in his pocket, and in 1958 started The new Kavli Institute for Systems Neu- the Centre for the Biology of Memory as Kavlico Corporation in Los Angeles, in the roscience was formally dedicated on August a prestigeous Kavli Institute in 2007. The United States. The company made sensors 14, 2007, when then-Minister of Education centre is one of only 15 designated world- for planes, automobiles and space applica- and Research Øystein Djupedal signed an wide, and the only one in Norway. The des- tions. The company was valued at more than agreement with Rector Torbjørn Digernes ignation means that the Institute will receive $300 million in 2000, when Kavli sold the at the Norwegian University of Science and approximately NOK 7 million in yearly firm and used the proceeds to found the Technology (NTNU) and with Fred Kavli. support for the foreseeable future, along Kavli Foundation to support research in “It’s always good to come home to Trondhe- with enormous international recognition. nanosciences, neurosciences and astrophys- im, but today it’s even better,” said Djupedal, ics. Fourteen Kavli Institutes have been who then expressed how proud he was that “The reason we chose CBM is because of founded in the last several years; Harvard, NTNU had become the newest member of their exceptional work in the neurosciences. Cambridge, Stanford, Yale, Caltech, Peking the small, highly exclusive group of universi- In its field, this group is known the world and MIT are among the universities where ties that hosts the Kavli Institutes. over. Experts have said that CBM’s work Nobel Prize winners are working at Kavli is some of the best that has been done in Institutes. Fred Kavli is now known the “I am delighted to establish this institute, 25 years,” said Fred Kavli to the Internet world over as a billionaire philanthropist, which we expect to make great future research newspaper Forskning.no. and is often described as “the new Nobel”. contributions toward further advancing He serves on a number of influential boards the basic knowledge and understanding Fred Kavli grew up in Eresfjorden in Roms- and commissions, including the U.S. Presi- of the brain,” said Fred Kavli. Noting that dal and studied physics and engineering dent’s Council of Advisors on Science and the institute is being established at his at the Norwegian Institute of Technology Technology. alma mater, Kavli added, “I think it’s also (NTH), as it was then known. In 1955 he

Fred Kavli (foreground), with Minister of Education and Research Øystein Djupedal (centre) and NTNU Rector Torbjørn Digernes (left) in a ceremony marking the establishment of the Institute. (Photo: Thor Nielsen/NTNU Info)

 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory important to note that, while it is an added tion and Research have promised to match pleasure establishing this institute at a the proceeds that the institute gets from place that provided me many fond personal its initial Kavli investment. In total, the re- The Kavli Foundation memories, that is not why this institute is search group will receive an annual amount being introduced here. It is because of the of approximately NOK 7 million. The Kavli Foundation sup- world-class neuroscience research being ports scientific research, conducted by scientists such as Edvard and Among other efforts, the new Kavli centre honours scientific achievement, May-Britt Moser.” will focus on a new method that uses the and promotes public under- “The new institute will give the centre the tools of molecular biology to turn brain cells standing of scientists and their best possible research opportunities, which on and off, which will make it much easier work through an international will increase our ability to recruit and keep to determine what individual cells actually program of research institutes, outstanding international researchers. Ad- do in the brain. “This is a newly developed professorships and symposia ditionally, the creation of the institute rep- method that will probably revolutionize in the fields of astrophysics, resents substantial recognition and acclaim this field of research. Now we can devote nanoscience and neuroscience. for the work being done at the Centre for ourselves to this fully. We will also work The Foundation also supports the Biology of Memory,” said an extremely with simulations and models of the brain,” the , which begin- pleased NTNU rector, Torbjørn Digernes. said Edvard Moser. ning in 2008 will recognize the world’s outstanding leaders in Extremely selective astrophysics, nanoscience and The Kavli Institute for Systems Neu- neuroscience. roscience will be headed by Edvard and May-Britt Moser, who also will continue There are now 15 Kavli leading NTNU’s Centre for the Biology of institutes worldwide dedicated Memory. The centre and institute will co- to neuroscience, nanoscience, exist, with the intent of eventually consider- astrophysics or theoreti- ing a new centre that would be a part of the cal physics. The Norwegian Kavli Institute. institute is the fourth Kavli institute dedicated to neuro- “This has great significance in a number of science, joining the Kavli Insti- ways. The Kavli Foundation is extremely tute for Neuroscience at Yale selective in its choice of specialist groups, University, the Kavli Institute and the other institutes are the best in their for Brain Science at Colum- field in the world. To be a member of this bia University, and the Kavli select group gives us enormous visibility and Institute for Brain and Mind recognition. Additionally, support for the at the University of , institute in principle lasts forever. That gives San Diego. us confidence in terms of secure basic re- search funding, which makes it possible for us to undertake a little more risky research. That also means we can make a great deal of progress in areas where we might have to wait many years to get results,” said Edvard Moser.

Developing new methods The foundation donates start-up funds of approximately NOK 45 million to each new Kavli Institute. The intent is for the money to be invested, with the institute drawing on yearly dividends for research support. The Kavli Foundation also requires that the host university for the research group provide significant financial support. In that regard, both NTNU and the Ministry of Educa-

Fred Kavli (Photo: kavlifoundation.org)

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory  Menno Witter becomes new member of KI-CBM

Professor Menno Witter began at the lived and worked in Trondheim now for specific to that area, is to use brain imag- Centre for the Biology of Memory in almost half a year, it feels like I have been ing approaches such as magnetic resonance September 2007 as a professor of neuro- able to continue and expand the already very imaging. This is now used to test functional anatomy, although he was officially hired in productive and influential collaboration we hypotheses related to differences between the beginning of January. Professor Witter have established over the years”, he says. hippocampus and parahippocampus, with is quite pleased with his new position in the eventual goal to differentiate between Trondheim. Menno made it no secret that the main different subareas of the hippocampus and reason why he chose NTNU was his desire parahippocampus. I have established a “The centre provides one of the world’s best to return to full-time research. collaborative effort with the MI centre at environments in which to do research on NTNU, where the focus is to develop tech- the hippocampus and parahippocampus “It is a pleasure to be able to spend much nology and paradigms to find differentiation and their relationships with other parts of more time on research. Of course, it is not within the hippocampus. I also supervise a the brain as a major substrate for learning really full-time, since I do have teaching PhD student in Amsterdam who is focusing and memory, so I feel honored and really obligations, but since my teaching activities on differentiations within the parahippoc- fortunate to be part of the team. Having mainly focus around neuroscience it feels ampal domain. He will join the NTNU MI like I am spending almost all of my time on center as a postdoctoral student later this what I like best, neuroscience”, he says. year. To me this is just another logical exten- sion from structure to function. Moreover, His research goals are also in line with my skills as a neuroanatomist can be quite Menno Witter the work being done by the CBM’s Moser instrumental to imaging, since I can be of group. assistance in interpreting where brain activa- tion is found related to certain behaviors”, Menno Witter is a professor of neuroana- “The aim of my group is to understand he says. tomy at Centre for the Biology of Memory the relationships between how neuronal / Kavli Institute for Systems Neuroscience. networks are wired up, and their function. Witter’s neuroanatomy laboratory is state- The structures we are interested in are all of-the-art, and is almost up and running. Menno Witter holds a part-time position involved in learning and memory processes, The lab will be fully functional with both at the VU University Medical Center Am- as far as we know. We also have strong indi- people and equipment in place in 2008; sterdam to conduct postdoctoral teaching cations that their individual contributions two technicians joined Menno a year ago, and research on the effect on the develop- to learning and memory are different, yet and the time is now right to fill the lab with ing brain of hormone treatment in young most likely complementary, and we know more colleagues. children, with a focus on overall cognitive that the wiring of their individual networks abilities, specifically learning. is very different. So, based on information “Most likely 3 – 4 new colleagues will join about how brain structures are wired, can us in 2008. We currently have two techni- He also has a visiting professorship at the I formulate hypotheses on function? Those cians who started to work with me in the Graduate School for Life Sciences, Tohoku hypotheses then should be tested, for exam- first quarter of 2007, after taking their ini- University in Sendai, Japan, where he works ple using the Mosers’ approaches. Of course, tial training for about 4 months in Amster- on optical imaging of parahippocampal- the process works the other way around as dam. We have also attracted the interest of hippocampal networks and the develop- well. If they have an idea about a specific quite a few students both from the medical ment of new tracing tools (genetically function, can we look for anything particu- faculty (students with a research focus) as modified viruses) for anatomical lar in the network that may be related to or well as students with different backgrounds experiments, in addition to teaching. explain that function?”, he wonders. through the master’s program, which indicates that neuroanatomical research may He has a lectureship at the University Witter’s approach to understanding the very well be attractive to young researchers, of Murcia, Spain in the PhD training brain is building the bridge between the ba- providing them with good career opportuni- programme, with a specific emphasis on sic research that the Moser group performs, ties because of my group being part of the Alzheimer’s disease. and the clinically oriented research of other centre”, he observes. parts of the medical faculty. Additionally, Witter has established a The technicians have a background in number of other formal international col- “If one has a specific idea/hypothesis about biophysics, and Menno emphasizes the laborations, and has worked as a consultant what parts of the hippocampal and parahip- importance of, and need for, different on projects on parahippocampal-hippocam- pocampal areas are doing, one promising scientific backgrounds in his lab. “These pal functions and electrophysiology with a new way to test those hypotheses, aside different backgrounds actually provide the number of research groups in the USA. from searching for patients that have lesions ability to operate instruments that will allow

10 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Discussing confocal data in the new microscope lab (Photo: Mentz Indergaard/NTNU-Info)

us to get started combining more biologi- research student, and in October my first the group is reaching the approximate size I cal approaches with the rather complicated post-doc arrived, who has a background in had in mind. It also has sufficient variation equipment that we are using, such as confo- invertebrate neuroanatomy and physiology. I with respect to background to facilitate cal laser scanning microscopy, electron had a PhD student in Amsterdam, paid for scientific discussions”, he adds. microscopy, in vitro electrophysiology, and, by CBM, who graduated from the master’s in 2008, voltage sensitive dye imaging. programme in neuroscience in Amsterdam. They have helped enormously in setting up She visits Trondheim to work at the centre the new lab, from all the ordering that is now and then. We have accepted a PhD involved, all the way from paper and gloves, student who will start in March, who has through chemicals up to equipment such as background training through the master’s scales and freezers” he says. programme in neuroscience at NTNU. In April we will employ a second post-doc who Students have already started working in has a PhD in neuroscience and metabo- his lab, and Menno is currently tutoring one lism, and in the course of the year I hope to ‘research student’ and a post-doc. His group employ two more post-docs; one with expe- will grow during 2008, and by next Christ- rience in optical imaging and in vitro elec- mas it will have reached what he thinks is trophysiology, and one with a background in the right size. neuroanatomy. With all the people in place and some more master’s students who have “In August 2007 we were joined by a expressed an interest in joining, I feel that

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory 11 A confirmation of excellence

Stefan Leutgeb received 1.75 million Euro Stefan Leutgeb has received (NOK 14 million)from The European Rea- outstanding offers from other search Council’s “Starting Independent universities, as a result of his Researcher Grants” for his research project work at the centre, and will ‘Memory storage in distributed cell as- relocate during 2008. Direc- semblies and its dysfunction in Alzheimer’s tor Edvard Moser is proud disease’. ”The ERC award is a consequence of Stefan’s achievements and of the outstanding research environment understands Leutgeb’s desire that I have been able to work in during the to build a research group of past five years”, says Leutgeb. his own. Leutgeb himself ex- plains the next step like this:

”The ERC award is a con- Training for success sequence of the outstanding “Being in such an extremely successful research situation research environment that I makes it difficult to build a have been able to work in dur- research programme that is seen as independent while Stefan Leutgeb receives flowers from ing the past five years” remaining at the same place where one has Rector Torbjørn Digernes. been trained. When evaluating the success (Photo: Klaus Jenssen) Only about 3% of the proposals were fund- of the Kavli Institute in the long-term, the ed, making Leutgeb’s award an immense institute will also be measured by having Stefan Leutgeb’s research focuses on honour, and a confirmation of excellence. successfully trained and placed young re- building the bridge between basic and ap- “The university, the centre, and its directors searchers at other world-leading institutions plied research. “With my research moving have substantially contributed to enabling and by having built a scientific network towards clinical interests, and with my inter- an ERC grant to be awarded to a researcher that will influence neuroscience research for est in building collaborations with clinical from NTNU and the Kavli Institute”, says many decades. It is in the best interest of research and retain those witin the Kavli In- Stefan Leutgeb. He is a member of the the Kavli Institute as well as for my research stitute, there will be a closer link to clinical CBM faculty and leader of the Memory career in the long-term to continue with my questions, in particular as the Kavli Institute Consolidation and Alzheimer’s Disease own well-respected research programme”, becomes more prominent in international group. says Leutgeb. research efforts.

EU millions to the CBM International recognition The European Research Council’s “Start- Leutgeb’s application was among 559 that ing Independent Researcher Grants” is a were selected for further evaluation out of an new financing mechanism established as a original application pool of more than 9000. part of the basic research programme called Ninety-two of those 9000 applications were “Ideas”, which is funded through the EU’s from Norwegian host institutions. The high 7th Framework Programme. The effort is number of applicants illustrates that the directed towards up-and-coming young competition was extremely difficult, which researchers who are establishing their careers also means that there is a great deal of inter- in Europe, and is a kind of European “big national recognition associated with winning brother” to the “Young Investigator Awards” an award from the ERC. (YFF) from the Research Council of Norway. ERC’s individual “Starting Grants” Ayumu Tashiro was also recognized, with are capped at a maximum of 400,000 his application making the final round Euros yearly over four years; for all grants for possible funding in 2008. If Tashiro is combined, the programme’s total budget is awarded a grant, he will establish a virus NOK 15 million. Leutgeb’s application was lab in which he will combine multi-unit awarded close to the maximum possible recording and behavioural analysis with virus amount. mediated, cell-type-specific genetic manipu- lation of neuronal activity.

12 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Anticipates substantial progress may not give us a cure for Alzheimer’s, but it Leutgeb believes that there will be sub- will give us important knowledge on our way stantial progress in the treating various to finding one in the future” he adds. symptoms of the diseases like Alzheimer’s, but that it is difficult to predict whether the “In general, I already think that basic treatment options will be able to entirely research on memory serves a clinical inter- halt the disease progression, as one would est, since progress in treating diseases with expect from a cure. memory problems will increasingly depend on understanding the biology of the system. “Alzheimer’s disease is characterized by The award of the Nobel Prize this year many cellular and biochemical processes that to scientists who invented the transgenic lead to the loss of connections between cells, technology to generate disease models in and during later stages, to widespread cell rodents, recognized the major contribution death. Although these processes are eventu- that rodent systems have made to finding ally seen in many cortical regions, they are treatment for all diseases, not only those of limited to select regions during the early the brain”, Leutgeb concludes. phases. My research is meant to identify whether the limited onset in the entorhino- hippocampal system has early consequences on the functioning of cells that are con- nected to these areas”, he says.

Basic research and clinical interest “If a link is found, one would be able to test whether local dysfunction in this system might generate abnormal activity patterns that could be used for diagnosing the disease or even for selectively interfering with the disease while it is still contained to a small subregion of the cortex. Our basic research

Tashiro studies memory formation in the Outstanding Young Alumni dentate gyrus, a subregion of the hip- pocampus. His aim is to determine which The CBM postdoctoral fellow Jonathan memory processes require new neurons, Whitlock received the Outstanding Young dynamic patterns of activity that new Alumni Award from his college institution neurons express during memory-related in the USA. The award is given within 15 behaviour, and the influence of new neurons years of graduation to individuals who have on their downstream structure. Information shown “outstanding accomplishments and about the functioning of new neurons in the promise”. Whitlock was selected on the basis normal brain could contribute to the future of his graduate work at Brown University development of efficient therapeutic strate- and MIT, which was published in the gies for a variety of brain disorders. journal Science in 2006. The work was later listed by the editors of Science as one of the top 10 breakthrough discoveries of 2006.

Left: Ayumu Tashiro may receive funding for a new viruslab in 2008 (Photo: Gorm Kallestad/Scanpix) Jonathan Whitlock receiving Outstanding Alumni Award (Photo: Jonathan Whitlock)

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory 13 Honours and prizes to young CBM and KI researchers

Several young CBM researchers were The Eppendorf Prize Fridtjof Nansen Prize awarded prestigeous prizes in 2007. Marianne Hafting Fyhn, PhD was one of The 2007 Fridtjof Nansen Prize for young two finalists for the Eppendorf & Science researchers went to CBM researchers Mari- BNA Award anne Fyhn, PhD and Torkel Hafting Fyhn, Rosamund Langston accepted the British PhD, for their studies of the neurophysi- Neuroscience Association Postgraduate ological basis for the brain’s sense of loca- Prize for her PhD dissertation on the role tion. The Fridtjof Nansen Prize is awarded of the hippocampus in event memory in the to researchers who are not yet 35 years old rat. Langston examined the role that the hip- and who are either Norwegian or research- pocampus plays in episodic memory in rats. ers with permanent residency in Norway. She studied rats while they executed various The 2007 prize was handed out during the learning tasks, and combined her study with Norwegian Academy of Science and Let- temporary and permanent pharmacological ters’ annual meeting on May 3, 2007. The inactivation of the hippocampus. chairman of the board of the Nansen Fund and associated funds, Professor Arnoldus Schytte Blix, handed out the awards. CBM finalist Marianne Fyhn (right) and the first prize winner Rachel Wilson from For more than 100 years, the Nansen Fund Harvard Medical School in the United States, at the award ceremony of the Eppendorf and associated funds have played a signifi- Prize in San Diego. (Photo: Eppendorf) cant role in the development of Norwegian science. The Nansen Fund’s statutes require Prize for Neurobiology, which was awarded that the Fund’s earnings be used to advance in San Diego in the USA on November 5, scientific research, and to support the pub- 2007. The first prize was awarded to Rachel lication of scientific writings, the establish- Wilson from Harvard Medical School, but ment of prize requirements, the recognition Fyhn received very complimentary of outstanding scientific discoveries or comments on her essay ”The Grid Map in dissertations, and support for exceptional the Brain”. scientists in unfettered scientific pursuits.

Fyhn started her graduate work in neuro- biology at CBM in 2000. She performed in vivo recordings of spatially modulated neu- rons from the hippocampus and entorhinal CBM researcher Rosamund Langston was cortex of freely behaving rats and contrib- awarded the British Neuroscience Association uted to the discovery of grid cells, which Postgraduate Prize in 2007. are neurons in entorhinal cortex with a (Photo: Emma Wood). remarkable hexagonal activity pattern. Since receiving her PhD in 2005, she has been a The prize-winner showed how the storage postdoctoral fellow at the CBM. of memory in the brain’s cerebral cortex decides what is known from before; she also The Eppendorf & Science Prize for used tests that mimicked aspects of human Neurobiology acknowledges the increasing episodic memory. These types of results are importance of this research in advancing our important in the further study of the neural understanding of how the brain and nerv- basis for episodic memory and in establish- ous system function – a quest that seems ing a link between animal experiments and destined for dramatic expansion in the com- clinical experiments. ing decades, said the jury. Eppendorf is an international biotech company that develops, Fridtjof Nansen’s Prize for young researchers produces and distributes systems for use in went in 2007 to CBM researchers Marianne life-science research laboratories worldwide. Fyhn, PhD and Torkel Hafting Fyhn, PhD. The prizes were handed out by Professor Arnoldus Schytte Blix. (Photo: Scanpix)

14 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual accounts

Income

Transferred from 2006 -921 531

Grants Norwegian Centre for Excellence (SFF) 11 100 000 Other External projects 9 836 400

Contribution from the Norwegian University of Science and Technology S/O funding 1 527 000 Operational grants 1 666 666 Overhead 3 796 684 Total Income 27 005 219

Expenses Net personnel costs (including social benefits) 13 709 321 Overhead 3 796 684 Scientific equipment 1 869 109 Laboratory consumables 1 952 680 Other expenses 4 220 033 Total expenses 25 547 827 Transferred to 2008 for new equipment in expanded lab areas 1 457 392

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory 15 Who’s Who

The Board

Arnstein Finset, Menno P. Witter, Vegard Heimly Brun, Professor Professor Post doc University of Oslo (chairman) (retired) Visiting professors

Julie Feilberg, Carol Barnes, Marianne Fyhn, Associate Professor Professor Post-doc ProRector, University of Arizona, NTNU USA Stig Slørdahl, Bruce McNaughton, Torkel Hafting Fyhn, Professor Professor Post-doc Dean, Faculty of Medicine, University of Arizona, NTNU USA Jan Morten Dyrstad, Randolf Menzel, Laura Colgin, Associate Professor Professor Post-doc Dean, Faculty of Social Science Free University of Berlin, and Technology Managment, Germany NTNU Karel Jezek, The Advisory Board Richard G. M. Morris, Post-doc Larry Squire, Professor Professor University of Edinburgh, UK University of California Ole Paulsen, Dori Derdikman, San Diego, USA (chairman) Professor Post-doc Terry Sejnowski, Oxford University, Professor UK Howard Hughes Med Inst, Alessandro Treves, James Ainge, Salk Institute, San Diego, USA Professor Post-doc Erin Schuman, International School for Professor Advanced Studies, Italy California Institute of Research scientists Jonathan Whitlock, Technology, Los Angeles, USA Post-doc Earl Miller, Professor Stefan Leutgeb, Masachusetts Institute Group leader Natalia Kononenko, of Technology, Boston, USA Post-doc Faculty Jill Leutgeb, Research Scientist Rosamund Langston, Post-doc Edvard I Moser, Professor and director Ayumu Tashiro, Research Scientist May-Britt Moser, Professor and co-director

16 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Graduate students Master students Espen Sjulstad, Histology and electrode wiring Cathrin Barbara Canto, Charlotte Boermeester Alme, Ph.D. student Master Knut S. Grøn, Animal technician (part-time) (retired) Kirsten Brun Kjelstrup, Henriette Folkvard Hestvaag, Ph.D student Master Ellen Marie Husby, Technician Paulo Girão, Veslemøy Mæhle Hult, Ph.D. student Master Hege J. Tunstad, Technical team Pr Info Trygve Solstad, Ph.D. student Ingvild Hammer, Ragnhild Gisetstad, Bioengineer Technician Espen Joakim Henriksen, Ph.D. student Kyrre Haugen, Gudrun Kulbotten Sjøvold, Histology technician Head of office Charlotte Boccara, Ph.D. student Associated members Klaus Jenssen, Project students Electronics engineer Gerit Pfuhl, Ph.D. student Tora Bonnevie, Raymond Skjerpeng, Project student Programmer Hanna Mustaparta, Professor NTNU, Norway Adam Johnson, Haagen Waade, Project student (retired) Computer engineer Hanne Lehn, Ph.D. student Jørgen Sugar, Ingunn E. Bakken, Robert Biegler, Project student Senior executive officer (retired) Associate professor NTNU (Psychology), Norway Magdalene Schlesiger, Ann Mari Amundsgård, Project student Histology and animal care

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory 17 Publications

Moser group CA3 synchronize with fast and slow gamma cific experiences? Society for Neuroscience rhythms in CA1. Society for Neuroscience Abstracts 33, 744.16. Fyhn, M., Hafting, T., Treves, A., Moser, Abstracts 33, 93.4. E.I., and Moser, M.-B. (2007). Hippoc- ampal remapping and grid realignment in Fyhn, M.H., Hafting, T.F., Witter, M.P., entorhinal cortex. Nature, 446, 190-194. Moser, E.I., Moser, M.-B. (2007). Grid cells Leutgeb group in medial entorhinal cortex of mice. Society Leutgeb, J.K., Leutgeb, S., Moser, M.-B., for Neuroscience Abstracts 33, 93.5. Leutgeb, S. and Leutgeb J.K. (2007). Pat- and Moser, E.I. (2007). Pattern separa- tern separation, pattern completion, and Hafting, T.F., Fyhn, M.H., Moser, M.-B., new neuronal codes within a continuous tion in dentate gyrus and CA3 of the Moser, E.I. (2007). Experience-dependent CA3 map. Learn. Mem., 14: 745 - 757. hippocampus. Science, 315, 961-966. backward shift of entorhinal grid cells. Soci- ety for Neuroscience Abstracts 33, 93.6. Moser, E.I. (2007). Atlas on our shoul- ders. Nature, 409, 406. Canto, C.B., Kwag, J., Hafting, T., Fyhn, Witter group M., Mann, E.O., Moser, E.I., Moser, M.-B., Leutgeb, J.K. and Moser, E.I. (2007). Witter, M.P., Paulsen, O. (2007). Rate-to- Witter MP (2007) The Perforant path. Enigmas of the dentate gyrus. Neuron, 55, phase transformation in layer II principal Projections from the entorhinal cortex to 176-178. neurons of the rat medial entorhinal cortex. the dentate gyrus. In: The Dentate Gyrus: Society for Neuroscience Abstracts 33, 93.7. A Comprehensive Guide to Structure, Dickson B & Moser EI (2007). Editorial Function and Clinical Implications H. overview: Neurobiology of Behaviour. Leutgeb, S., Colgin, L.L., Jezek, K., Leutgeb, Scharfman (Ed). Progr. Br. Res, 163: 43- J.K., Fyhn, M., McNaughton, B.L., Moser, Current Opinion in Neurobiology 17, 672- 61, Elsevier Ltd Oxford. 674. E.I., Moser, M.-B. (2007). Path integration- based attractor dynamics in the entorhinal Witter MP (2007). Intrinsic and extrinsic Moser, E.I. and Moser, M.-B (2007). Grid cortex. Society for Neuroscience Abstracts 33, 93.8. wiring of CA3; Indications for connec- cells. Scholarpedia, 2:3394. tional heterogeneity. Learn. Mem. 14: Leutgeb, J.K., Leutgeb, S., Tashiro, A., 705-713. Neuroscience Abstracts Moser, E.I., Moser, M.-B. (2007). The encoding of novelty in the dentate gyrus and Papp G, Witter MP, Treves A (2007) Kjelstrup, K.G., Solstad, T., Brun, V.H., CA3 network. Society for Neuroscience The CA3 network as a memory store for Fyhn, M., Hafting, T., Leutgeb, S., Witter, Abstracts 33, 93.9. spatial representations. Learn. Mem. 14: M., Moser, M.-B., Moser, E.I. (2007). Very 732-744 large place fields at the ventral pole of the Henriksen, E.J., Leutgeb, S., Barnes, C.A., hippocampal CA3 area. Society for Neuro- Witter, M.P., Moser, E.I., Moser, M.-B. Spa- Wouterlood FG, Canto CB, Aliane V, science Abstracts 33, 93.1. tial modulation along the proximodistal axis Boekel AJ, Grosche J, Hartig W, Belien of the subiculum. Society for Neuroscience JAM, Witter MP (2007) Coexpression of Solstad, T., Brun, V.H., Kjelstrup, K.G., Abstracts 33, 93.10. Fyhn, M., Moser, E.I., Moser, M.-B. (2007). vesicular glutamate transportes 1 and 2, glutamic acid decarboxylase and calretinin Grid expansion alonog the dorso-ventral Lehn, H., Steffenach, H.-A., Moser, E.I., axis of the medial entorhinal cortex. Society in rat entorhinal cortex. Brain Struct Moser, M.-B., Witter, M.P., Veltman, D.J., Funct. 212: 309-319. for Neuroscience Abstracts 33, 93.2. Haraldseth, O. (2007). Robust activation of hippocampal and parahippocampal Hagenbeek RE, Rombouts SA, Veltman Brun, V.H., Leutgeb, S.., Wu, H.-Q., cortices in individual subjects during recall Schwarcz, R., Witter, M.P., Moser, E.I., of autobiographical memories. Society for DJ, Van Strien JW, Witter MP, Scheltens Moser, M.-B. (2007). Entorhinal layer III Neuroscience Abstracts 33, 93.11. P, Barkhof F. (2007) Non-linear changes lesions impair place representation in CA1 in brain activity durng continuous word but not CA3. Society for Neuroscience Buzzetti, R.A., Marrone, D.F., Schaner, repetition: an event-related multi-para- Abstracts 33, 93.3. M.J., Chawla, M.K., Bohanick, J.D., metric study. Amer. J. Neuro Radiol. 28: Khoboko, T., Seymor, A.W., Leutgeb, J.K., 1715-1721. Colgin, L., Denninger, T., Fyhn, M., Haft- Leutgeb, S., Moser, E.I., Moser, M.-B., ing, T., Jensen, O., Moser, M.-B., Moser, McNaughton, B.L., Barnes, C.A. (2007). Geurts JG, Bö L, Roosendaal SD, Hazes E.I. (2007). Medial entorhinal cortex and Do dentate gyrus granule cells tag time-spe- T, Daniëls R, Barkhof F, Witter MP, Hu-

18 Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory itinga I, van der Valk P (2007). Extensive hippocampal demyelination in multiple sclerosis. J Neuropath Exp Neurol 66: 819-827.

Jones BF, Witter MP (2007). Cin- gulate cortex projections to the (para)hippocampal region in the rat. Hip- pocampus 17: 957-976.

Cappaert NLM, Wadman, WJ, Witter MP (2007). Spatiotemporal analyses of interactions between entorhinal and CA1 projections to the subiculum in rat brain slices. Hippocampus 17: 909-921.

Scher AI, Xu Y, Korf ESC, White LR, Scheltens P, Toga AW, Thompson PM, Hartley SW, Witter MP, Valentino DJ, Launer LJ (2007) Hippocampal shape analysis in Alzheimer’s disease: a popula- tion-based study. Neuroimage, 36: 8-18.

Tse D, Langston RF, Kakeyama M, Bethus I, Spooner PA, Wood ER, Witter MP, Morris RGM (2007). Schemas and memory consolidation. Science, 316: 76-82

Neuroscience Abstracts

M. de Boer, M. van der Roest, R. Diez, S. te Slaa, M. P. Witter, A. B. Mulder. Towards neural coding of attentional processes in mouse prefrontal cortex. Soc. Neurosci. Abstr (2007) : 741.7

N. M. van Strien, N. L. M. Cappaert, M.P Witter An interactive diagram of the anatomical interconnectivity of the rat pa- rahippocampal-hippocampal network. Soc. Neurosci. Abstr (2007) : 93.12.

F. G. Wouterlood, V. Aliane, C. B. Canto, A. J. Boekel, E. Hur, P. Barroso-Chinea, W. Hartig, L. Zaborsky, J. L. Lansiego, M. P. Witter Intrinsic and thalamic origin of calretinin-VGluT2 innervation of entorhi- nal cortex in the rat. Soc. Neurosci. Abstr (2007) : 93.13

Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory Annual Report 2007 – Kavli Institute and Centre for the Biology of Memory 19 Photo, frontpage: Floris G. Wouterlood and Amber Boekel

Annual Report for KI-CBM 2007 E-mail: Telefax: Telephone: NO-7489 Trondheim, Norway Medical-Technical Research Centre, Centre of Excellence Centre for the Biology of Memory Kavli Institute for Systems Neuroscience and thought of, and creative solutions that change our daily lives. arts. Cross-disciplinary cooperation results in ideas no one else has from the social sciences, the arts, medicine, architecture to fine natural sciences as well as in other academic disciplines ranging Trondheim represents academic eminence in technology and the The Norwegian University of Science and Technology (NTNU) in NTNU – Innovation and Creativity

contact +47 73 59 82 94 +47 73 59 82 42 @ cbm.ntnu.no www.ntnu.no/cbm