Annual Report 2011 Annual Report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

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Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory Annual report 2011 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

The KI/CBM staff, March 2012. (Photo: Matias Okawa)

Front page: The cover image shows the firing rate plot of a single entorhinal grid cell, with blue indicating a low firing rate and red indicating a high firing rate. The different spatial scales of grid cells along the dorsal-ventral axis of the medial entorhinal cortex suggest the presence of multiple spatial maps, as represented by the mosaic appearance of the grid cell. Illustration: Lisa Giocomo

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contents NTNU The protein that controls the brain’s “zoom fuction” ...... 2 Kavli Institute for Systems Neuroscience and Centre for Bats have grid cells, too ...... 4 the Biology of Memory Two neurons in the same pub are not necessarily friends ...... 6 Eric Kandel receives honorary doctorate from NTNU...... 8 ERC Grant to May-Britt Moser...... 8 NORBRAIN receives MNOK 80 grant...... 9 ”Teleportation” shows that memories have a quantal nature...... 10 Norway has a new brain centre ...... 12 Nordic and European awards go to KI/CBM leaders ...... 13 Excellent results give SPACEBRAIN an afterlife ...... 14 ”Undoubtedly excellent research” ...... 15 The media loves brain science ...... 16 KI/CBM broadens into new research areas ...... 17 Who’s who at KI/CBM...... 18 Annual accounts ...... 23 Publications...... 24 Centre of Excellence Medical-Technical Research Centre The Biology of Memory and Systems Neuroscience ...... 25 NO-7489 Trondheim, Norway

Telephone: + 47 73 59 82 42 Telefax: + 47 73 59 82 94 E-mail: [email protected] Internet: ntnu.no/cbm

Annual Report published by the Kavli Institute for Systems Neuro- science and Centre for the Biology of Memory. KI/CBM – a brief history

Editor: Director Edvard Moser The Centre for the Biology of Memory (CBM) was established at the Norwegian University of Science and Technology (NTNU) in 2002 as a Centre of Excellence (CoE) Text: with funding for ten years from the Research Council of Norway. Bjarne Røsjø, BR Media Hege Tunstad, KI/CBM In 2007, the Norwegian-American physicist, businessman, billionaire and philanthropist Translation: Fred Kavli selected CBM as one of 15 prestigious Kavli Institutes. The CBM is the Nancy Bazilchuk, Bazilchuk Ink only Norwegian institute to be thus honoured to date. The appointment means the department gets about NOK 7 million in annual support from the Kavli Foundation Layout & print: for the foreseeable future, in addition to tremendous international recognition. Fagtrykk, NO-7005 Trondheim As a result of its history, the centre now has two names: the Kavli Institute for Systems Number printed: Neuroscience and the Centre for the Biology of Memory (KI / CBM). After 2012, when 400 the CoE period expires, the centre will “only” be the Kavli Institute for Systems Download: Neuroscience. The Norwegian Ministry of Education and Research has indicated a ntnu.no/cbm/publications willingness to continue with funding after the CoE period ends.

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The protein that controls the brain’s “zoom function” The brains of rats and mice make mental maps of their surroundings at multiple levels, from coarse overviews to fine- grained, detailed maps. Researchers at the KI/CBM have shown that a specific protein controls the brain’s “zoom function”: If the protein does not work, the brain loses its ability to create detailed maps.

In 2005, KI/CBM researchers discovered edition of the scientific journal Cell, that the brains of rats contain grid cells, researcher Lisa Giocomo and colleagues which are specialized neurons that work at the KI/CBM described how they together to create a grid for the mental knocked out a specific kind of ion channel map that a rat makes of its surroundings. in the grid cells in the brains of mice. The grid in the rat brain bears an amazing When the HCN1 channels were disabled, resemblance to the coordinate lines on the resolution of the maps created a normal map, except that the grids in by the brain became coarser. “This is a rat’s map are triangular instead of comparable to losing every other longi- square. Grid cells are found in the part tude and latitude line on a regular map, of the brain called the entorhinal cortex. which would mean you wouldn’t get a Lisa Giocomo came to the KI/CBM in Trondheim good representation of the environment as a postdoctoral fellow in 2008 and now leads Four years after this finding, KI/CBM re- at a detailed level,” Giocomo explains. a research group at the Institute. (Photo: Lisa searchers discovered that the grid cells Giocomo) in the rat brain create a number of different maps of varying resolution, from The neuron’s power supply thousand in a grid cell. Entorhinal grid coarse overview maps that cover larger cells have a much higher proportion of areas, to maps where the grid’s “mesh” The ion channels in cell membranes HCN channels compared to many (but not is much finer and contains many details. can be described as the neuron’s power all) other types of neurons in the brain. It was later shown that grid cells are supply. “If the cell is compared to a light also found in mice and bats, and there bulb, then turning on an ion channel Researchers at the KI/CBM have thus are indications that they are found in can be thought of as supplying a little found that a small part of the grid most species of mammals. bit more electricity to the light bulb. cells’ power supply, specifically the ion And if enough ion channels are active, channels known as HCN1, regulates or the right combination is active, you the neuron’s ability to create detailed Detailed maps disappear ‘ll get enough electricity to turn on maps of the animal’s surroundings. But the light bulb. But a neuron is much what do all of the other ion channels All cells – including grid cells – are more comp licated than a light bulb, of do? Giocomo doesn’t know the answer surrounded by a biological membrane course,” Giocomo adds. yet, but she would like to find out more. that separates the cell’s interior from “There are a lot of obvious follow-up its external environment. Among other A grid cell or any other type of neuron questions to this research. Maybe there things, the cell membrane includes a that is “turned on” by the electrical cur- are other types of ion channels that are number of channels or pores that regu- rents through ion channels is then in a contributing to the larger scale maps in late the transport of ions (electrically position to react by firing an electrical the brain, or maybe there are entirely charged atoms or molecules) in and out signal – an action potential - to another other types of mechanisms that are of the cell. These ion channels often neuron. Action potentials are the tech- generating the larger scale representa- consist of a single protein, and researchers nique that cells use to communicate tions of the environment,” she suggests. at KI /CBM are now studying which func- with each other. tions can be controlled by the channels. There are thousands of individual ion Head of a new Kavli group Everybody knows how to zoom in and channels in a single neuron. No one out on an online map to get the level of knows for certain how many of them are Lisa Giocomo completed her PhD at resolution you need to get you where HCN1 ion channels, but there might be Boston University in 2008 with a project you want to go. In the 16 November 2011 several hundred to as many as a few that focused on examining how the grid

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HCN1+/+ HCN1-/-

N C N C

Dorsal Entorhinal Grid Cell

Ventral Entorhinal Grid Cell

Entorhinal grid cells are reminiscent of a longitude and latitude coordinate Grid cells are found in the entorhinal cortex, which is found in system. The scale of the brain’s grid map is set by HCN1 channels, so close proximity to the hippocampus in the brain of rats, mice when HCN1 is lost, the resolution of the grid map is decreased. and other mammals. (Illustration: Lisa Giocomo) (Photo: Lisa Giocomo) cells in the entorhinal cortex communi- researchers at the Kavli Institute for Another aspect of the story is that the cate. It was during this work that she be- Brain Science at Columbia University in same mice that lost the ability to create gan to suspect that the HCN1 channels New York. The institute is headed by detailed maps of their surroundings play an important role in the formation Professor Eric Kandel, who won the Nobel have been shown to perform better at of grid cells. Later in 2008, she came to Prize in Physiology or Medicine in 2000. a different kind of task. Researchers at the KI/CBM as a postdoctoral research Eric Kandel’s laboratory have demon- fellow with Edvard and May-Britt Moser The mice without an HCN1 ion channel strated that if the mice are placed in a to pursue the question further. When were developed using genetic engineering so-called Morris water maze, which is Giocomo’s postdoc was completed, she by the Kavli Institute in New York, which a water-filled basin with a platform that became the head of her own research also investigated the effect of missing is hidden under the surface, the mice group, which in the future will continue ion channels in the place cells in the that lacked the HCN1 channel were to focus on the cellular mechanisms hippocampus. Place cells are thought to actually better at remembering where underlying spatial memory. base their spatial response on the calcu- the platform was located. The recent lations of the grid cells. “We believe that study by Giocomo and colleagues dem- Lisa Giocomo’s findings could prove use- this is a great example of collaborative onstrated that while their mental maps ful for future research on Alzheimer’s research. We discussed and debated had become larger, they also became and related diseases, particularly our findings and gave each other lots of more stable. “We believe this increase in because the area that is damaged in feedback and input,” says Edvard Moser, stability helps the mice navigate better Alzheimer’s is the same area that she director of the KI/CBM at NTNU. in certain types of spatial tasks,” says is investigating. “One of the first things Giocomo. to go wrong with Alzheimer’s is that you suddenly start to lose your sense of direction. We do not know yet if there is Facts about the entorhinal cortex any connection between Alzheimer’s and The entorhinal cortex is located in close proximity to the hippocampus, a key the mechanisms we are studying, but it centre for episodic memory. hippocampus. At the bottom of the entorhinal might be worth looking into,” she says. cortex, near the bottom of the mouse brain, are the grid cells that mark points that are at a distance from each other. The ever-finer and denser grids are created by the grid cells that are higher up in the entorhinal cortex. Two cooperating Kavli Institutes “It is tempting to think that you need the densest networks to operate over short The article in Cell was published simul- distances with high resolution, and that the largest mesh sizes are necessary for taneously with a companion article in the long distances. But I rather think that the different grid mesh sizes have to be scientific journal Neuron, authored by combined to enable the animal to navigate well,” says Edvard Moser.

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Bats have grid cells, too

Menno Witter at the KI/CBM and two Israeli scientists have discovered that the brains of bats have cells that create a grid in the animals’ mental maps of their surroundings. The discovery confirms the assumption that grid cells are found in most mammals, and sheds new light on theories of how this cell type is formed.

Grid cells have been previously found passes by well-defined points in the in the brains of rats and mice, which environment. The combined signals adds importance to the discovery by the from the grid cells form a triangular and The Egyptian fruit bat is an impressive animal Norwegian-Israeli research group in Chinese checkers-like network that is with a wing span that averages 60 cm. Grid cells 2011 that this cell type also is found in rolled out over the environment when in bats fire electrical signals that that combine Egyptian fruit bats (Rousettus aegypticus). an animal navigates. The signals from to create a triangular grid of the animal’s The discovery was published in the grid cells are sent to the hippocampus environment. (Photo: Michael Yartsev and Nachum Ulanovsky) scientific journal Nature on 3 November and the so-called place cells, which fire 2011, in an article written by Professor electrical signals each time the animal Menno Witter at the KI/CBM in colla is in a specific area of the environment. oration with Professors Michael M. In other words, grid cells draw a kind of Yartsev and Nachum Ulanovsky at the coordinate system, while the place cells Weizmann Institute of Science in Israel. are specific to a particular environment by an average interval of 37 seconds. and mark where the animal is at any We found that the variation in the theta “Bats are in a mammalian order which, time in relation to the coordinates. frequency oscillations in bats did not seen from a phylogenetic and evolution- correspond to any changes in the firing ary perspective, is far from rodents. It has hitherto been a mystery as to how properties of the grid cells. The reason- This finding thus confirms the assump- the grid cells are formed, but researchers able conclusion is that the grid cells tion that grid cells are a widespread have launched two major competing in bats are not derived from the theta phenomenon among mammals. The theories. One of the theories suggests that rhythm,” explains Witter. assumption is also confirmed by the fact the spatial periodicity of grid cells is in that the brains of all mammals are built some way related to the theta rhythm, the same way in the areas where we find which is a prominent hippocampal-entor- grid cells,” explains Professor Witter. hinal network oscillation – a brain wave Will test flying bats – in the 6–10 Hz frequency range. The The Egyptian fruit bat is found in the studies of the Egyptian fruit bats contra- Middle East and Africa outside of the Two grid cell theories dict this theory, because the bats lack Sahara, and is often considered a pest the clear theta rhythms seen in rodents. because a flock can strip a fruit tree Grid cells are specialized neurons in the bare in just minutes. These fascinating mammalian brain and were discovered “The theta frequency oscillations in animals are equipped with a sonar sys- by researchers at the KI/CBM in 2005. rodents are almost continuous when tem similar to the one used by insect- Grid cells in rats, mice, and now bats the animal is moving around, and they eating bats to locate bugs, but the fruit have been found in the part of the brain disappear when the animal stops. The bats use sonar to determine whether a called the entorhinal cortex, and what bats have only sporadic and intermittent fruit is ripe. makes these cells special is that they theta frequency oscillations, typically fire electrical signals when an animal with one-second-long bursts separated The experiments with fruit bats were

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conducted in Nachum Ulanovsky’s of view. “The demonstration of grid Professor Menno Witter laboratory in Rehovot outside Tel Aviv, cells in the absence of detectable theta leads one of the five research teams at the on animals that were crawling around oscillations in Egyptian fruit bats is a KI/CBM in Trondheim. looking for food. Proponents of the theta fresh input which undoubtedly will guide (Photo: Geir Mogen/ frequency oscillation theory have argued theoretical and experimental studies in NTNU) that the animals were not moving at the the coming years. It would be extremely right speed for the theta frequency oscil- surprising if a dual set of mechanisms lations to start, and that the frequency resulted in grid cells with exactly the with which the cells fire would essen- same properties and an identical func- tially mask the theta rhythm. Professor tional organization,” the two believe. Witter disagrees.

“We essentially did two things sequen- What is the mechanism? tially. We started by analysing the activity in the grid cells during the period when The theory about theta waves as a driv- we did see theta oscillations, and ing force behind grid cells is thus weak- compared this information to activity in ened. But what then is the mechanism? the grid cells during the period with no “We feel that the so-called attractor such oscillations. There was no obvious network theory has become a more difference in the results from both plausible candidate. The theory states samples. Secondly, we did a statistical that the grid patterns are generated analysis of grid cell data in the rat, in from local network activity, but we can’t “Previously, we investigated how rats, which we resampled data such that the be sure about this before we have con- mice and crawling bats navigate, but neurons would show a firing frequency ducted more experiments,” Witter says. in that case what we are talking about in rats similar to what we observed in in principle is navigation in two dimen- the bat. The result was that even in the Nachum Ulanovsky and Michael M. sions on a surface. The experiments case of such low firing frequencies, the Yartsev are now at work on a new with bats can provide answers as to neurons would still show the properties approach in which they will investigate whether grid cells also create a grid in of grid cells. Therefore, we feel that the activity of grid cells in bats as they three dimensions. We will also get an the data observed in Israel are a really fly. This research presents major answer as to whether theta waves occur strong argument against the oscillatory technical challenges, because it will not in bats when they fly instead of crawl,” model,” explains Witter. be possible to connect a cable from the explains Witter. animal’s head to a computer. Researchers The KI/CBM’s Lisa Giocomo and Edvard must instead use a small wireless Moser wrote a commentary and ex- transmitter on the fruit bat’s head. People also navigate pressed strong support for Witter’s point Several international research groups are currently investigating whether Hippocampus there are grid cells in other animal The hippocampus is a small structure at the bottom of the mammalian brain, species, and there have been published closely connected to the entorhinal cortex. The hippocampus plays a very studies that suggest that they exist in important role in the brain and is also essential for the sense of place and both humans and primates in general. memory. Researchers at the KI/CBM hope that studies of the hippocampus But the verdict is not in yet on this and the sense of place can also lead to a deeper understanding of memory – research. which can create a better understanding of the brain’s functioning. “There is certainly no doubt that we humans have a navigation system, and it Brain Waves is reasonable to assume that the system Brain waves occur when the billions of neurons in the brain communicate with is linked to the hippocampus and entor each other using small electrical impulses (action potentials) that fluctuate in hinal cortex too. Research on rodents time. Hippocampal theta waves in rats have a frequency range of 6-10 Hz and and bats can therefore contribute to appear mainly when the animal is engaged in active motor behaviour such as increased knowledge about how the walking or exploratory sniffing. human brain works,” concludes Witter.

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Two neurons in the same pub are not necessarily friends

It’s no easy task recording the electrical signals from multiple firing neurons in the brains of rats and mice, but figuring out the configuration of the underlying neuronal networks is even more of a challenge. “The problem can be compared to figuring out who are real friends in a group of people at the pub,” explains Yasser Roudi.

The physicist Yasser Roudi came to the Correlation is not a proof of Simply by finding that two neurons fire KI/CBM in 2010, with the purpose of connection together, one cannot infer that they are establishing a new research group dedi- necessarily connected,” Roudi says. cated to analysing and processing mas- One challenge is to figure out which sive amounts of incoming information signal comes from which specific neu- The problem of mapping the connections from an environment chock full of data, ron in a big group, but that problem has between neurons in the brain is similar like the brain. Roudi’s group is studying been solved to some degree by other to mapping the relationships among the issue from a theoretical point of researchers. Yasser Roudi’s research ten people who go to different pubs and view, using methods from the worlds of group is focused on a much more bars, adds Roudi. “You might assume mathematics and statistical physics. difficult question: They are using the re- that they are all friends, or you might corded signals to infer the connections think that one of them is a ‘hub’ that When Edvard and May-Britt Moser – the networks – between neurons. has invited nine friends who were not established the predecessor of the KI/ “Making that inference represents a previously acquainted with each other. CBM in Trondheim in 1996, the focus big leap forward: It allows us to find out In fact, you can have all sorts of different was to study the biological roots of how network properties influence the patterns of friendship among these memory by detecting and analysing firing of neurons, monitor how these people. We are trying to establish the electrical signals in the brain. The properties are modified through behav- connections between individual neurons human brain is an extremely complex iour, and thus eventually, how computa- in a group by looking at their electrical structure with approximately 100 billion tion is performed in the nervous system. signals, much like you could figure out the neurons, each connected to approxi- It is also a difficult question because friendships between people by looking mately 10 000 other neurons. The correlation is not a proof of connection. at their activity in a bar,” he explains. neurons use weak electrical signals – action potentials – when they communicate with each other. The researchers at the KI/CBM use the rat brain as a “stand-in” to make scientific models of the human brain.

One important technique used at the KI/ CBM is to insert tiny electrodes into the rat brain to record the action potentials from neurons. It is difficult enough to place one electrode with great precision in a brain and listen to the signals from a few cells, but the technique has now Histograms of couplings inferred by applying a non-equilibrium Ising model to synthetic data from a been advanced to the point that it is simulated cortical network (see Roudi & Hertz 11). Only the connections between excitatory neurons common practice to use multiple are shown. Putting a vertical line between the peaks as a decision boundary, we can reconstruct the electrodes for listening to several hun- network: an inferred coupling that falls on the right (left) of the line would be taken to indicate an dred or even thousands of networking excitatory (the absence of a) connection. B shows an example of such reconstruction for a subset of neurons at the same time. 20 neurons from a network of 1000 neurons. The true connectivity is shown in C. (Il.: Yasser Roudi)

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A hot topic allowed the analytical investigation of The relationship between activity and simulated cortical networks. We showed connectivity is a hot topic and has that when we look at data generated implications for the studies of systems from simulated cortical networks, the biology, genetic networks, protein dynamic models work a lot better than networks, neuronal networks, social equilibrium models,” explains Roudi. networks, and so on. “Our understand- The research community greeted the ing of biological networks has been very article as a breakthrough and its publi- limited because until recently, experi- cation has already spurred other groups mental tools only allowed us to study to take up the approach. the properties of one or a few elements at a time. Luckily, technological breakthroughs and advances have changed Models of Grid Cells and Path this situation. Biologists can now use Yasser Roudi received his PhD from the Inter- national School for Advanced Studies (SISSA) state-of-the-art technology to look at Integration in Trieste in 2005. He is now a corresponding many elements of a biological network at Yasser Roudi’s group is also active in fellow at the Nordic Institute for Theoretical the same time. But there is still a major another line of research that aims at Physics (NORDITA) in Stockholm and a research problem: What do we do with the data building computational models of the group leader at the KI/CBM. (Photo: Yasser that we get using these modern tools? entorhinal cortex and the hippocampus, Roudi) This is where statistical physics becomes to better understand the generation important. Statistical physics is the dis- of grid cell firing and path integration. to studying spike trains recorded in live cipline that has been developed over the In this effort, and in collaboration with animals. We will use the recordings to last century to deal with large systems Edvard and May-Britt Moser and Menno infer functional connectivity, and then we of interacting elements,” Roudi says. Witter, Roudi uses knowledge about will build computational models based the anatomy of these networks to make on those connections. The models can Roudi’s basic idea is to start with data realistic models of them and to relate then be used for analysis and designing from multiple electrode recordings of the output of the models to what could new experiments. We hope that this will action potentials in a rat brain, delivered be measured in vivo. It is not surprising give us a better understanding of the by researchers from Edvard and May- that this line of research is related to general principles of network operation Britt Moser’s group. They then try to and benefits from efforts to solve the in complex systems, and will also allow reverse engineer the network that could network inference problem. us to learn more about the formation have generated the signals. and function of grid cells,” Roudi adds. “Our present knowledge about the way “We are in fact building digital models of neurons interact with each other, to a networks of neurons, and then we tweak large extent, comes from in vitro record- The brain as a machine the models until they send signals that ings, where researchers have found are similar to those that were recorded,” connections from studying slices of Yasser Roudi’s work is truly inter he says. brain tissue under a microscope,” Roudi disciplinary, because he uses statistical says. “But connectivity in the living brain and physical methods that could equally is constantly modulated by behaviour be used to study the mixing of gases A dynamic approach and cognitive processes, so in vitro or chemicals in a solution. “You might connectivity may be very different from say that I am studying the brain as a Most researchers in Roudi’s field have in vivo connectivity. This is a particularly machine, which is possible because the until now mainly been focused on the important issue in parts of the brain general laws of physics apply across study of equilibrium systems, but these such as the hippocampus, where memory all of nature. This is also the reason are very far from biological systems. formation through modification of syn- why different sciences can benefit from Yasser Roudi and John Hertz from aptic connectivity is the main function. exchanging tools with each other. My NORDITA and the Niels Bohr Institute Therefore, we are now trying to use the aim as a scientist is to use the laws of in Denmark introduced a new approach technological breakthroughs in multi- physics to further our understanding of in 2011, with an article in the academic unit spike recordings in a completely information processing and of computa- journal Physical Review Letters. “What new way. To put it simply, we are trying tions in the brain as far as possible,” we did was to build a platform that to go from studying in vitro connectivity Roudi says.

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Eric Kandel receives honorary doctorate from NTNU

Professor Eric Kandel at Columbia University in New York was awarded an honorary doctorate by the Norwegian University of Science and Technology (NTNU) in 2011. Kandel is a Nobel Prize winner and a close associate of the KI/CBM.

Eric Kandel is a senior investigator at spread that the “rock star of brain the Howard Hughes Medical Institute, a science” had visited Trondheim. professor of neuroscience, biochemistry and biophysics at Columbia University, Professor Kandel started studying sea and a Fred Kavli professor and director slugs in 1962 and was able to show how of the Kavli Institute for Brain Science at learning is caused by changes in the Professor Eric Kandel was named an honorary Columbia. synaptic connections between specific doctor at NTNU in 2011. (Photo: Thor Nielsen/ neurons, and what cellular mechanisms NTNU Info) Dr. Kandel collaborates with members are responsible for simple forms of of the KI/CBM on cellular mechanisms short-term and long-term memory of spatial map formation in the brain, formation. His more recent work has and has visited the Trondheim research shown that these mechanisms are and our understanding of brain function community on several occasions. He universal across species. more generally. He has been recognized has given three public lectures at NTNU. with a long list of honorary degrees and The first lecture – about the cellular Eric Kandel’s work, stretching over a awards, including the National Medal mechanisms of memory – caused so period of more than 50 years, has had an of Science in the United States and the much excitement that the regional enormous influence on our understanding Nobel Prize for Physiology or Medicine newspaper announced in a two-page of how memory is generated in the brain, in 2000. ERC Grant to May-Britt Moser Professor May-Britt Moser was awarded an Advanced Investigator Grant from the European Research Council (ERC) in November 2010. The grant goes to the funding of a research programme that started in 2011 and runs to 2015.

The ERC Advanced Grant is considered and experiences are represented in a international recognition at the highest short-term time domain and how groups level, and will provide €2.5 million towards of cells (ensembles) involved in one May-Britt Moser’s research projects representation fade into those associ- over five years. Professor Moser will ated with another. also receive additional financial support from NTNU, which together will give the The ERC’s Advanced Investigator Grant KI/CBM NOK 5 million (€0.62M) extra is linked to the EU’s 7th Framework per year until 2015. Programme for research. Professor Edvard Moser received an ERC Advanced The grants will fund a broad research Investigator Grant in 2008. programme, ranging from the basic phenomenology of the transition between hippocampal representations to the role Professor May-Britt Moser’s research at the KI/ of gamma oscillations, thalamic activity CBM is financed by an Advanced Investigator and anatomy and development. The Grant from the European Research Council until aim is to determine how environments 2015. (Photo: Geir Mogen/NTNU)

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NORBRAIN receives MNOK 80 grant

The Norwegian Brain Initiative received MNOK 80 in a grant from the Research Council of Norway in October 2011. The contribution will be used to set up state-of-the-art neuroscience equipment to enable a broad spectrum of molecular and systems neuroscience research in Trondheim and Oslo.

The idea behind the Norwegian Brain Post doctoral researcher Initiative – NORBRAIN – is that neuro- Jonathan Couey uses mul- science is one of the fastest-developing tiple simultaneous patch areas of science, on the brink of dis- clamp recording in brain covering the mechanisms for complex slices to quantify synaptic connectivity in the MEC. mental functions. We will soon be able Understanding the local to understand how neurons enable us to microcircuit from which think, decide, remember, and feel, and grid patterns emerge will be how these processes may fail during essential to understanding disease. For this potential to be realized, how this neuronal computa- however, scientists need to change the tion is performed by the way they do their research. It is neces- brain. (Photo: Geir Mogen/ sary to establish research platforms for NTNU) scientists with complementary skills and insights, and it is necessary to combine forces. These scientists must also NORBRAIN is an NTNU-coordinated “The aim is to build one of the best have access to high-cost state-of-the- national infrastructure for neuroscience. neuroscience infrastructures in the art equipment needed to address the The project is structured around two world, with the equipment made avail- most fundamental questions in the field. Centres of Excellence – the KI/CBM at able to neuroscientists from the whole NTNU and the Centre for Molecular of Norway. The project has an inter Biology and Neuroscience at the University national aspect as well, in that it makes A coordinated national initiative of Oslo – as well as one Centre for it easier for us to welcome guest re- Research-based Innovation – the Medical searchers and researchers in training,“ This was the background for the Imaging Laboratory (MI-Lab) at NTNU. Professor Edvard Moser says. Norwegian University of Science and Technology (NTNU) and the University of The timing of the RCN grant was very Oslo’s decision in 2010 to work coop- One of the best infrastructures favourable because new space will be eratively to establish NORBRAIN as a available at the beginning of 2012 for national infrastructure for neuroscience The grant provides an unprecedented NORBRAIN at all three host centres. research. Professor Edvard Moser and opportunity for coordinated investment NTNU has converted its Medical NTNU coordinated a joint application to in the kinds of high-cost state-of-the- Technology Centre into a Brain Centre, the Research Council of Norway, which art equipment needed to sample large which is home to the expanding KI/CBM had announced the availability of NOK amounts of data at high resolution and as well as the MI Lab and other groups. 400 million for competitive grants for at a high rate over large numbers of The University of Oslo is building an new large-scale research infrastructure synapses, cells and brain systems. The annex to Domus Medica, which will house investments. In November 2011, the two approach will give researchers the tools the CMBN and activities developing universities got the good news that the and data they need to understand the around the centre. Research Council had granted NOK 80 fundamental mechanisms of brain func- million (€10.2 million) to NORBRAIN. tion and dysfunction.

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“Teleportation” shows that memories have a quantal nature

Memories are divided into discrete individual packets, analogous to the way that light is divided into individual bits called quanta. The brain can swap between different memories as often as eight times in one second, and different memories are not mixed.

Researchers at the KI/CBM showed in 2011 that memories are “quantal,” meaning that they are organized into small packages, and that memories do not come in a continuous stream. Instead, the brain can switch between different memories in just 125 milliseconds, and two different memories are kept separate, even though they might The brain does not create gradual transitions between similar memories, says seem quite similar to each other. The Karel Jezek.Photo: Karel Jezek new findings were published in Nature in September 2011, in a scientific article with a former postdoc at KI/CBM, Doctor Karel Ježek at the Institute of Physiology Memories of past Christmases This is similar to a rat remembering that of the Academy of Sciences of the Czech it has been looking for food in two differ- Republic, as the first author. The new article in Nature built on results ent rooms,” says May-Britt Moser. from 2004, when researchers in The study of how memories are organized Trondheim explained how the hippo But how does the brain call up the correct at the millisecond level has received campus and the brain can distinguish memory out of the chaos of competing support from the European Research between memories that seem similar memories? Researchers at the KI /CBM Council Advanced Investigator Grant, to each other. “The ability to distinguish decided to investigate this further and which was awarded to Professor May- memories of one Christmas Eve from came up with a new and intricate chal- Britt Moser in 2011. “There are no another is due to the encoding of the lenge for their research rats in Trond- gradual transitions between memories. different memories in different networks heim. The eager animals first hunted The brain will not let itself get confused. of neurons in the brain. But the memor for chocolate bits in a dark box that had It never mixes different places and ies of various Christmas evenings also a lighted pattern on the floor, and then memories together, even though share many similarities and are stored again in another dark box that had a you might perceive it that way,” says in the same area of the brain, so that you lighted pattern on one wall. While the Professor Moser. can quickly ‘switch’ between memories. rats hunted for treats, the memories of

10 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

the two places were stored in two differ- flickered several times between the two May-Britt Moser does not exclude the ent but similar networks of nerve cells different memories. The flickering could possibility that there may be more grad- in the hippocampus. last up to several seconds, but eventu- ual transitions between memories within ally the rat brain decided which room each theta cycle. The research published it was in, and the flickering stopped. It in 2011 showed that memories could mix “Teleporting” rats turned out that the memories were not to a certain degree during the first part mixed while the flickering was going on. of the cycle, but in the second part of the The two spaces were then converted to a There was no gradual transition between cycle, the hippocampus was completely single room in which the landmarks and memories of the two places, which led engaged with one or the other memory. patterns could be controlled by an elec- to the conclusion that memories come in tric switch. After the rats had learned packets or quanta. their way in the two variants of the same A clock frequency in the space, the researchers could simply It turned out that the packets lasted for “teleport” the rats from one space to 125 milliseconds. This corresponds to a hippocampus another by flipping a switch. This re- time interval known as the theta cycle, sulted in a conflict where the rat’s visual which was discovered approximately 50 Edvard and May-Britt Moser now sug- system told it that it was in a new place, years ago. Theta cycles are formed when gest that the theta wave acts as a kind of but the number of footsteps it had taken, many cells in the hippocampus send clock that coordinates memories in the the smell of the box, and other variables electrical signals (action potentials) at hippocampus. Neurons in the hippo said that it was still in the old one. the same time, and then are silent at campus are not very receptive to signals the same time. This coordinated activity from other cells when they are in their The researchers measured the electrical gives rise to measurable brain waves. quiet phase. “Without this kind of clock, activity of as many as 100 neurons in the However, it has not previously been everything would soon be chaotic, with CA3 section of the hippocampus during shown that the brain is able to call up an cells that could not talk to each other and right after the rats were “tele entire memory in as short a period as because they were out of step,” ported”, and saw that the rat brain first the duration of a theta wave. Professor Edvard Moser said in an article on the Norwegian research website Forskning.no. Stepping out onto the wrong floor The Trondheim scientists suggest that this system of theta waves and flickering The teleportation effect in rats is similar between different memories is specific to the momentary disorientation you to the memory and the hippocampus, would feel when the elevator doors and it is unlikely that similar systems open and you step out onto the wrong will be found in many other places in the floor. The disorientation occurs because brain. In the hippocampus, for example, the place you expect to see and the the brain can take the time it needs to place you actually do see are mutually find the right memory, because it is to exclusive. the animal’s benefit. However, reaction time in the visual cortex can be critical Normally, the brain orients itself to survival, particularly if the animal is gradually as you move around. The unable to identify a danger in an unam- hippocampus contains place cells, which biguous way in just a few milliseconds. record both your environment and your movement within it, in order to form The researchers hope to look at other memories that ensure you always know brain oscillation patterns in the future, where you are. To update the brain on such as the gamma wave, which repeats your position, place cells fire in a rhythm itself several times faster than the theta Researchers at the KI/CBM tricked rats into called a theta oscillation or cycle, which wave. believing that they had been teleported, and discovered that memories have a quantal nature. repeats every 125 milliseconds and (Credit: Håkon Fyhn / Kavli Institute for Systems is especially prominent when you’re Neuroscience / NTNU) moving.

11 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Norway has a new brain centre

“Here in Trondheim you have created a research environment that excels internationally,” said Minister of Research and Higher Education Tora Aasland, as she laid the cornerstone for the Norwegian Brain Centre in Trondheim on 10 January 2011.

When it was first founded, the KI/CBM support this effort in the future. I hope financed with contributions from the was located in NTNU’s Medical Technical the new centre will continue to evolve Research Council of Norway, the Euro- Research Centre. With the migration and find new answers that can benefit pean Research Council (ERC), the Kavli of a number of other research groups society,” Minister Aasland said. Foundation and the EU’s Framework to the new University Hospital of Programme. Trondheim in 2010, NTNU was able to invest NOK 42 million to establish the More space, upgraded Norwegian Brain Centre (NorBC), which The Prime Minister was will encompass the KI/CBM. The goal of standards the new centre is to become the world’s impressed largest laboratory for the measurement The expansion plans call for NorBC’s of electrical activity in neural networks. area to expand by nearly tenfold to well The Norwegian Prime Minister Jens The investment represents a continu over four thousand square meters, Stoltenberg was very enthusiastic when ation of NTNU’s long-term commitment while at the same time the overall he inaugurated the new research centre to brain research, with the KI/CBM at standard for the labs will be upgraded. on 28 February 2012. ”This has been a the forefront. The centre will explore a wide range of fascinating visit, and I shall remember methodological approaches to under- that this is a world leading institution The cornerstone laid by Tora Aasland standing how the brain’s networks func- in the field of brain research,” Stolten- is a crystal with a reconstruction of a tion. The researchers started moving berg said. Professor May-Britt Moser real brain cell from a rat. “I am proud into the new facilities in January 2012. thanked the Prime Minister and gave of what you have achieved and can In addition to NTNU’s contribution, the him an extra brain cell, or more pre- promise that the government will also research activities at NorBC will be cisely a model of a brain cell from a rat.

The Norwegian Prime Minister Jens Stoltenberg was very enthusiastic when he opened the new research centre. (Photo: Matias Okawa)

12 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Nordic and European awards go to KI/CBM leaders

Professors May-Britt and Edvard Moser were awarded two prestigious awards in 2011, the Swiss-based Louis-Jeantet Prize for Medicine and the Norwegian-based Anders Jahre’s Award for Medical Research. The dual awards rank the researchers among the best in their field in both Scandinavia and Europe.

Edvard and May-Britt Moser were the sense of place, and all deserve a bit awarded the 2011 Louis-Jeantet Prize of credit. We are also very pleased by the for Medicine for their pioneering work economic aspect of the prize. It gives us related to the discovery of grid cells and the ability to launch ambitious research the mechanisms underlying the sense for which it can be difficult to find regular of place in the brain. The prize was funding,” the researchers said in an shared with the German biologist Stefan interview with the regional Norwegian Jentsch, director of the Max Planck newspaper Adresseavisen.

Institute of Biochemistry in Martinsried. The Louis-Jeantet Prize for Medicine was The Louis-Jeantet Prize for Medicine is Torbjørn Digernes, rector of the presented to May-Britt and Edvard Moser at a awarded annually to the best European Norwegian University of Science and ceremony in Geneva on 14 April 2011. (Photo: scientists in biology and biomedicine, Technology (NTNU) in Trondheim, con- FONDATION LOUIS-JEANTET) and provided the researchers in Trond- gratulated the professors, saying that heim with more than NOK 4.2 million the prize makes him proud. “May-Britt to outstanding Nordic researchers in (SF 700,000). and Edvard Moser are talented and basic and clinical medicine. dedicated scientists who repeatedly put Trondheim and NTNU research on the “Their findings have received broad Support for more research world map,” Digernes said. international recognition since they provide a new understanding of how the The prize is awarded by a foundation that brain works. With support from the Kavli was established in the Swiss city of A Nordic honour Foundation and the Research Council of Geneva in 1982, after the French busi- Norway (Centre of Excellence) the two nessman Louis Jeantet bequeathed his Edvard and May-Britt Moser were also scientists have established a very strong entire fortune to the effort before he died recognized with the 2011 Anders Jahre’s research environment in Trondheim and of cancer in 1981. The purpose of the Award for Medical Research, which is succeeded in attracting many research- prize is to focus on the basic biological valued at NOK 1 million and is awarded ers from abroad,” the citation for the research that may some day be of award said. importance in medicine and medical research.

Edvard and May-Britt Moser say that the prize will be used to continue their search for the sense of place in the brain, with a special emphasis on examining how grid cells work together with other cells in the entorhinal cortex and hippocampus. The two are very grateful for the recognition associated with the award of the Louis-Jeantet Prize. University of Oslo Rector Ole Petter Ottersen and University Director Gunn-Elin Aa. Bjørneboe pre- “There is a large group of researchers sented the Anders Jahre Senior Medical Award to May-Britt and Edvard Moser on 14 October 2011. who have worked to identify the basis for (Photo: Francesco Saggio, University of Oslo)

13 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Excellent results give SPACEBRAIN an afterlife

The aim of the EU-funded SPACEBRAIN project was to study how complex mental functions originate from electrical and chemical processes. The project was so successful that the participants decided to continue to work cooperatively even after the end of the funding period.

link between macroscopic and microscopic levels in the brain. Forty-two months of collaboration have produced significant advances in our understanding of how space is represented in neural networks of the entorhinal cortex and hippocampus, brain regions known to form internal maps of the local environment. Two papers with SPACE- BRAIN funding have been published or accepted for publication in Nature, three in Science, one in Cell, and several are appearing in other high-impact journals such as Nature Neuroscience and Nature Methods. Key scientific advances include, first of all, new insights into the intrinsic wiring of the entorhinal cortex, according to the final report.

A project with unique features

Members of the EU-funded SPACEBRAIN consortium held their fourth annual meeting in Stechelberg “The success of the project reflects in the Swiss Alps from 15 to 17 June 2011. (Photo: Karel Jezek) several unique features of SPACEBRAIN. One is the integration of experimental and theoretical work. From the begin- The project Space coding in hippocampo- blocks at the microscopic level, and to ning, experimentalists and modellers entorhinal neuronal assemblies phenomenological descriptions at the have been working on complementary (SPACEBRAIN) started in 2008 with macroscopic level. We know much less subprojects, exchanging information as funding from the European Union’s about the link between these levels – soon as data or models were avail- Seventh Framework Programme (FP7) how complex mental functions originate able. Another is the explicit attempt to for research, and formally ended with from electrical and chemical processes,” combine methods and concepts from a fourth annual meeting in the Swiss explains Professor Edvard Moser, director multiple levels of analysis, ranging from Alps in June 2011. The group decided of the KI/CBM. He was the project’s mechanisms of synaptic transmission to continue with a fifth meeting in 2012, coordinator from start to finish, and is to interactions between large distrib- in Heidelberg, despite the fact that the very happy with the results. uted circuits. Finally, the success also funding period is over. reflects the open and positive working atmosphere of the consortium. Trust “Despite impressive advances in almost Breaking new ground and an open attitude have formed the every field of neuroscience, our under- basis for constructive discussion and standing of brain function has largely The SPACEBRAIN project broke a lot of true collaboration from the first day of been confined to the brain’s building new ground in the understanding of the the project,” concludes Edvard Moser.

14 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

“Undoubtedly excellent research”

The scientific quality of the research conducted by the KI/CBM is “undoubtedly excellent”, according to an international evaluation carried out on behalf the Research Council of Norway.

The Research Council of Norway (RCN) The evaluation was led by Professor research institutions in Sweden, carried out a comprehensive evaluation Ulf Lerner at Umeå University and the Denmark, the United Kingdom, Canada, of Norwegian research in biology, University of Gothenburg, Sweden. Poland and France. medicine and health in 2010 and 2011. The other eight members came from The evaluation panel concluded that the scientific quality at the KI/CBM is “undoubtedly excellent”, and that the centre has developed into “one of the world’s leading arenas for experimental and theoretical studies of memory in brain networks”.

According to the evaluation, the KI/CBM Evaluation of Biology, Medicine and has been able to provide some of the Health Research in Norway (2011) most groundbreaking insights so far Report of the Principal Evaluation Committee into how spatial location and spatial memory are computed in the brain Evaluation and, more generally, how the brain Division for Science generates its own neural patterns. The Molecular Biology Botany, Zoology evaluation panel was also impressed Panel 3 and Ecology-related Diciplines by the societal impact of the research Panel 1 in Trondheim. In addition to the general importance of truly excellent neuro Public Health and Clinical Research science research, the present pro- Health-related Panel 4B Research gramme also addresses particular Panel 5 aspects of importance for understanding and diagnosing Alzheimer’s disease, the Clinical Research Physiology-related Panel 4A Disciplines report says. Panel 2

The recommendation is that the funding should be continued after the Centre of Psychology and Psychiatry Excellence award from the RCN expires Panel 6 in 2012. The members of the evaluation panel are confident that the importance of continued funding is understood by the Norwegian University of Science and Technology, the RCN and the Norwegian Government and “will be addressed in good time”. The KI/CBM has developed into one of the world’s leading arenas for experimental and theoretical studies of memory in brain networks, according to an international evaluation in 2011. (Cover page of RCN Report)

15 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

The media love brain science

Everyone is interested in the brain, if last year’s media attention to research conducted at the KI/CBM is any indication. More than 90 articles were written in the Norwegian media in 2011 about the institute and its research. There were nearly the same number of articles published in the international online media.

The Nordic media monitoring agency great deal of media discussion because Cat”, which took as its starting point the Retriever listed a total of 23 articles on they were finalists in the competition for unique memory of Trondheim Symphony the KI / CBM in the print editions of the honour of being named “Trøndelag Orchestra conductor Krzysztof Urbanski, various Norwegian national newspapers residents of the year”, which is awarded who can memorize an entire musical over the year. There were also 26 articles by the regional newspaper Adresseavisen score in minutes. Moser drove a sports in the online editions of different and the Norwegian Broadcasting Corpo- car with Urbanski to try to figure out why national newspapers, 42 articles in the ration’s (NRK) regional Trøndelag office. a man with such a good memory has a print editions of Norwegian regional and very poor sense of location. local newspapers, and approximately Norwegian regions and counties have a 90 articles in the online media in the strong tradition of friendly rivalry, and Perhaps the biggest media event in Nordic region and internationally. the regional newspaper Sunnmørs 2011 came on Friday 7 October, when posten appreciated that the couple Edvard and May-Britt Moser participated Many of the editors at home and abroad were highly valued in the neighbouring in NRK broadcaster Fredrik Skavlan’s were intrigued by the report that the KI / county. Edvard and May-Britt Moser are eponymous talk show, “Skavlan”. The CBM researcher Lisa Giocomo and originally from Hareid and Fosnavåg in talk show often has more than 1 million colleagues had “found the zoom button Sunnmøre County. viewers in Norway and Sweden. The

in the brain.” Professor May-Britt LarsArne Nilsen frå MylnemeisterTor- couple were guests in the studio along StordogVolda bjørn Nesved Volda er trenar forHødd Lidenskap og ElektriskeMylne i Levande Moser’s research attracted attention fotball adecco engasjement Volda, kulturhistoriewith the Swedish actress Noomi Rapace, 06.04,2011 september 2006 as far away as India, where theHE large LGBrain scienceFoto:Knut Arne Aar- on TV HELG 28 the SwedishHELG 34 Foreign Minister Carl Bildt online newspaper The Hindu wrote that and the American singer Tony Bennett.

“Memories come in packages AG - eight Edvard Moser was a participant in NRK’s times a second.” The same news on the popular programme “Schrödinger’s

Italian La Stampa website wasLØRD 9.givenapril 20the11 Nr.84128.årgang Pris kr 20,-

Ola Einang er tilsettved Høg- title “Il nostro Cervello divide isk ulenRicordiiVolda 2008

in pacchetti as 125 millisecondi”,Foto:Knut whileArne Aarset the online South Africa Star newspaper asked the timely question, “Did I sleep in my bed this time?”

Prizes and investments Sponsa fattig-jente Everest-gjengen frå The Norwegian media were also1985 veryhar beta lt lege- utdanninga til dattera til taxisjåføren dei interested in the establishmentbruk ofte i1the985.– Ho var så sterk itrua på at ho Norwegian Brain Centre (NorBC)skulle atbli lege ,atvitok henne på orden, seier NTNU, and the awarding of theOla Swiss-Einang iVolda. NYHETER 8 based Louis-Jeantet Prize for Medicine The Norwegian media were very and the Norwegian-based Anders interested in the awarding of Maskefall åpner for Jahre’s Award for Medical Researchet ærlig møt toem ed the Swiss-based Louis-Jeantet segselv og andre Edvard and May-Britt Moser. SYNNØVE HOPE Får pris på4,2 Prize to Edvard and May-Britt KULTUR 1 Moser. (Photo: Elisabeth Lund/ ND LU Sunnmørsposten)

The Mosers were also the subject of a ABETH LIS :E

millioner kroner TO FO Ineste ukemottar forsker paretMay-Britt og Edvard Søknadsfrist: 15. april deltid |samlinger |nett Moser den prestisjetunge Idrettens Louis-Jeantet prisen på 4,2 Administrasjon, planlegging og ledelse 16 Digital kompetanse tjener i40år millioner kroner for sin bane- Estetiske fag OlavHansen fraDimna Idrett og friluftsliv IL sin innsats forfri- Helse- og sosialfag idrettengjennom 40 år brytende hjerneforsking. Historie, kultur,samfunn og religion ble markertmed pris. GOMRÅDER Lærer- og førskolelærerutdanning, spes. ped.

FA Språk og litteratur SPORT 8 HELG 19-23 Les mer på www.hivolda.no |T:70075018|E-post: [email protected] Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

KI/CBM broadens into new research areas

In 2011, the KI/CBM decided to intensify its focus on molecular and systems neuroscience, two fields that can describe how the network of neurons in the brain can work together.

When May-Britt and Edvard Moser in 1996 established the research that has evolved into today’s KI/CBM, the focus was on studying the biological roots of memory by recording and analysing electrical signals in the brain. The centre later expanded its activities to include molecular biology studies, and in 2009 the institute was further expanded with the establishment of a research group working on modelling and computational neuroscience. In 2010 the centre also began to develop virus-based techniques that can be used to turn on and off the activity of certain nerve cells, as well as developing a new technology for measuring the microscopic signals inside cells.

Beginning in 2012, the KI/CBM will intensify its focus on molecular and systems neuroscience as a tool in brain research. The institute has invited appli- cations for a new faculty position in systems neuroscience. The institute is open to applicants with experience and inter- est in using state-of-the-art molecular and cellular technologies to understand neural networks and behaviour.

Molecular biology and systems neuroscience are essential tools to expand the understanding of neural networks and their behaviour neural networks and their behaviour. Here, Albert Tsao, a PhD candidate at the KI/CBM, works with a laser to be used in an optogenetic experiment. (Photo: Geir Mogen/NTNU)

17 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Who’s who at KI/CBM

CBM Board Advisory Board

Bjørn Hafskjold Larry Squire Dean Faculty of Natural Professor University of Sciences and Technology California San Diego, USA Lisa Giocomo NTNU (chairman) Group leader

Jan Morten Dyrstad Terry Sejnowski Dean of Faculty of Social Professor Howard Hughes Sciences and Technology Medical Institute, Salk Institute, Yasser Roudi Management NTNU (chairman) USA Group leader

Stig Slørdahl Erin Schuman Dean Faculty of Medicine Professor Max Planck Institute Sheng Jia Zhang NTNU for Brain Research, Germany Group leader

Tore O. Sandvik Earl Miller County Council Chair, Professor Massachusetts Sør-Trøndelag County Institute of Technology, USA Visiting professors

Alessandro Treves Professor International School Kavli Board Faculty for Advanced Studies, Italy

Bruce McNaughton Kari Melby Edvard Moser Professor University of Prorector NTNU (chairman) Professor and Director Lethbridge, Canada

Carol Barnes May-Britt Moser May-Britt Moser Professor University of Arizona, Professor NTNU Professor and Director USA

Menno Witter Menno Witter Mayank Mehta Professor NTNU Professor Associate Professor UCLA, USA

Stig Slørdahl Ole Paulsen Dean Faculty of Medicine Professor University of NTNU junior group leaders Cambridge, UK

Randolf Menzel Ayumu Tashiro Professor Free University of Group leader Berlin, Germany

18 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Richard Morris Professor University of Aree Widya Witoelar Kally O’Reilly Edinburgh, UK Postdoc Postdoc Roudi group Witter group

Alexandre Daniel Surget Kang Zheng Postdoc Postdoc Research scientists Tashiro group Witter group

Debora Ledergerber Calvin Young Noriko Kogonezawa Postdoc Postdoc Researcher Moser group Tashiro group Witter group

Emilio Kropff Masato Uemura Rafal Czajkowski Postdoc Postdoc Postdoc Moser group Tashiro group Witter group

Hiroshi Ito Nils Borgesius Postdoc Postdoc Moser group Tashiro group on sabbatical leave

Homare Yamahachi Raveendran Rajeevkumar Nair Charlotte Alme Postdoc Postdoc PhD candidate Moser group Tashiro group Moser group

Jing Ye Takuma Kitanishi Trygve Solstad Postdoc Postdoc Researcher Moser group Tashiro group Moser group

Jonathan Whitlock Cathrin Canto Researcher Researcher Moser group Witter group graduate students

Kei Igarashi Hideki Kondo Albert Tsao Postdoc Postdoc PhD candidate Moser group Witter group Moser group

Tiffany Van Cauter Jay Jonathan Couey Charlotte Boccara Postdoc Postdoc PhD candidate Moser group Witter group Moser group

19 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Chenglin Miao Alessandro Luchetti Vania Cuellar PhD candidate PhD candidate Master’s student Moser group Tashiro group Giocomo group

Espen Joakim Henriksen Ingrid Amellem James Carmichael PhD candidate PhD candidate Master’s student Moser group Tashiro group Moser group

Hanne Stensola Mehdi Fallahnezhad Atefe Rafiee Tari PhD candidate PhD candidate Master’s student Moser group Tashiro group Tashiro group

Ingvild Kruge Stefan Matthias Blankvoort Katarzyna Anna Kapusta PhD candidate PhD candidate Master’s student Moser group Tashiro group Tashiro group

Li Lu Grethe Mari Olsen Magnus Helgheim Blystad PhD candidate PhD candidate Master’s student Moser group Witter group Tashiro group

Nenitha Charlotte Dagslott Ingrid Heggland William Espen Windsor PhD candidate PhD candidate Master’s student Moser group Witter group Tashiro group

Tanja Wernle Mathias Mathiasen Øystein Rød Brekk PhD candidate PhD candidate Master’s student Moser group Witter group Tashiro group

Tor Stensola Abdala Mumuni Ussif PhD candidate Master’s student Moser group Master’s Students Witter group

Tora Bonnevie Fan Zheng Annelene Gulden Dahl PhD candidate Master’s student Master’s student Moser group Moser group Witter group

Benjamin Adric Dunn Torgeir Wåga Asgeir Kobro-Flatmoen PhD candidate Master’s student Master’s student Roudi group Giocomo Group Witter group

20 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Christian Gjeraker Master’s student Unni Iversen Ingvild Hammer Witter group Senior executive officer Infrastructure Support group Support group

Christin H. Berndtsson Master’s student Merethe Andresen Witter group Animal care Technical team Support group

Hanna Haaland Master’s student Alice Burøy Tommy Åsmul Witter group Molecular biology Animal care Moser group Support group

Lilliane Hansen Ann Mari Amundsgård Naomi Kitanishi Master’s student Histology, hyperdrives Research assistant Witter group Moser group Tashiro group

Sobia Islam Endre Kråkvik Teruyo Tashiro Master’s student Molecular biology, hyperdrives Neurogenesis Witter group Moser group Tashiro group

Klaus Jenssen Bruno Monterotti Electronics Anatomy administration Moser group Witter group

Hege Tunstad Kyrre Haugen Paulo Girão Bettencourt Communication Officer Histology Anatomy Support group Moser group Witter group

Iuliana Hussein Raymond Skjerpeng Ragnhild Giestad Head of office Programming Anatomy Support group Moser group Witter group

Linda Veres Grethe Jakobsen Executive Officer Animal care Support group Support group Research Assistants

Marzena Grindal Haagen Waade Chika Yoshii Higher Executive Officer Computers, networks Research assistant Support group Support group Tashiro group

21 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Vanja Cnops Inge Storkaas Røysland Research assistant Project student Tashiro group Witter group

Yadira Ibarguen Juliane Kristine Andreassen Research assistant Project student Tashiro group Witter group

Ida Aasebø Jørgen Sugar Research assistant Project student Witter group Witter group

Juan Wu Øyvind Wilsgård Simonsen Research assistant Project student Zhang group Witter group

project students

Hannah Maria Eggink Project student Giocomo group

Paul Eduard Cornelis Mertens Project student Giocomo group

Eline Kristindatter Storm Project student Moser group

Kristian Frøland Project student Moser group

Tale Litlere Bjerknes Project student Moser group

22 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Annual Accounts 2011

Income

Transferred from 2010 6 886 000

Norwegian Research Council: Centre of Excellence 10 000 000

Norwegian Research Council: other 7 663 000

International (EU, ERC, Marie Curie, James McDonnell Foundation) 16 448 000

Other public/private (Kavli Foundation, Contact Committee) 1 035 000

Norwegian University of Science and Technology

Funding (RSO/Kavli/RD) 16 722 750

Own contribution BOA 6 882 607

Incentive funds EU/ERC 1 055 009

Total income 66 692 366

Expenses

Net personnel costs 35 304 000

Indirect costs including floorage 17 032 000

Scientific equipment 2 394 000

Operational expenses 12 211 000

Total expenses 66 941 000

Transferred to 2012 - 248 634

Amounts in NOK

23 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Publications

May-Britt og Edvard Moser Roudi Y., Hertz J. (2011). Mean Field Theory for Non-equilibrium Moser EI, Moser M-B (2011). Seeing into the future. Nature, Network Reconstruct Phys. Rev. Lett., 106, 048702 469, 303-304.

Moser EI (2011). The multi-laned hippocampus. Nature Menno Witter Neurosci. 14, 407-408. Kononenko N, Witter MP (2011) Presubiculum layer III conveys retrosplenial input to the medial entorhinal cortex. Hippo- Moser M-B, Moser EI (2011). Crystals of the brain. EMBO Mol. campus, DOI 10.1002/hipo.20949 Med. 3, 1-4. Kjonigsten LJ, Leergaard TB, Witter MP, Bjaalie JG (2011) Giocomo LM, Moser M-B and Moser EI (2011). Computational Digital atlas of anatomical subdivisions and boundaries of the models of grid cells. Neuron, 71, 589-603. rat hippocampal region. Front. Neuroinform. 5:2. doi: 10.33 9/ fninf.2011.00002. Moser EI (2011). A bat’s perspective on navigation. Proc. Natl. Acad. Sci., 108, 15665-15666. Sugar J, Witter MP, van Strien NM, Cappaerts NLM (2011) The retrosplenial cortex: intrinsic connectiviuty and connections Jezek K, Henriksen EJ, Treves A, Moser EI and Moser (2011). with the (para)hippocampal region in the rat. An interactive Theta-paced flickering between place-cell maps in the hippo- connectome. Front. Neuroinform. 5:7. doi: 10.3389/ campus. Nature, 478, 246-249. fninf.2011.00007

Giocomo LM, Hussaini SA, Zheng F, Kandel ER, Moser M-B Small, SA, Schobel SA, Buxton R, Witter MP, Barnes CA (2011) and Moser EI (2011). Grid cells use HCN1 channels for spatial A pathophysiological framework of the hippocampal circuit in scaling. Cell, 147, 1159-1170. aging and disease. Nature Rev Neurosci, 12: 585-601.

Giocomo LM, Moser EI (2011). Spatial representation: Maps in Yartsev M, Witter MP, Ulanovsky N (2011) Grid cells without a temporal void. Current Biology, 21, R962-R964. theta oscillations in the entorhinal cortex of bats. Nature, 479: 103-107.

Ayumu Tashiro Canto CB, Witter MP (2011) Cellular properties of principal Aasebø IE, Blankvoort S and Tashiro A (2011). Critical neurons in the rat entorhinal cortex. I. The lateral entorhinal maturational period of new neurons in adult dentate gyrus for cortex. Hippocampus, DOI 10.1002/hipo.20997 their involvement in memory formation. Eur J Neurosci, 33, p1094-100 Canto CB, Witter MP (2011) Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex. Hippocampus, DOI 10.1002/hipo.20993 Yassir Roudi Sakallariu J., Roudi Y., Hertz J., Mezard M. (2011). Effect of Witter MP (2011) The Hippocampus. In: The Mouse Nervous coupling asymmetry on mean-field solutions of direct and System. Eds G. Paxinos, L- Puilles & C. Watson. Acad. Press, inverse Sherrington-Kirkpatrick model. preprint ch. 5, pp 112-139.

Hertz J., Roudi Y., Tyrcha J. (2011). Ising Models for Inferring Witter MP (2011) Entorhinal cortex. Scholarpedia, 6(10):4380. Network Structure From Spike Data. “Principles of Neural Coding”, edited by Stefano Panzeri and Rodrigo Quian Quiroga, preprint Lisa Giocomo Giocomo LM, Hussaini SA, Zheng F, Kandel ER, Moser MB, Roudi Y., Hertz J. (2011). Dynamical TAP equations for non- Moser EI (2011). Increased spatial scale in grid cells of HCN1 equilibrium Ising spin glasses, J. Stat. Mech., P03031 knockout mice. Cell, 147:1159-1170.

24 Annual report 2011 Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory

Yoshida M, Giocomo LM, Boardman I, Hasselmo ME (2011). Giocomo LM, Moser EI (2011). Spatial Representation: Maps Frequency of subthreshold oscillations at different membrane in a temporal void. Current Biology, 21:R962-R964. potential voltages in neurons at different anatomical positions on the dorso-ventral axis in the rat medial entorhinal cortex. Giocomo LM, Moser MB, Moser EI (2011). Computational Journal of Neuroscience, 31:12683-94. models of grid cells. Neuron, 71:589-603.

Navratilova Z, Giocomo LM, Fellous JM, Hasselmo ME, Mc- Naughton BL (2011). Phase precession and variable spatial scaling in a periodic attractor map model of medial entorhinal grid cells with realistic after-spike dynamics. Hippocampus, 10.1002/hipo.20939

The Biology of Memory and Systems Neuroscience

Researchers at KI / CBM explore the The electrodes don’t need to be inserted researchers found cells that function brain’s functioning by detecting and directly into the nerve cells, but instead like a compass and a speedometer. analysing the electrical signals in the are placed gently in the space outside brain. In 2009, KI / CBM also began of the cells. Each electrode can then The discovery of a completely new type an active expansion into genetics and record the electrical activity in many of brain cell that registers borders and molecular biology in order to increase brain cells at once, but the electrodes barriers caused scientific excitement its tool box for studies of neural network are so sensitive that it is possible to worldwide when it was published in the actions in the performing brain. distinguish between the different signals American journal Science in 2008. In the from each individual neuron. same year, it was also discovered that Since the centre’s inception, KI / CBM the hippocampus has an inbuilt map researchers have used laboratory rats with a number of different scales. as study animals. The rats run around A series of important findings in boxes and corridors in search of food In 2009, researchers at the KI/CBM and have very thin electrodes inserted The KI/CBM has produced a series of discovered both that the brain uses into their brains, primarily in the regions sensational scientific findings. In its different wavelengths to separate of the brain called the hippocampus first year, researchers found that direct experiences, and that the brain is able and entorhinal cortex. This enables inputs from the entorhinal cortex to the to create its own library of maps for researchers to detect brain activity. hippocampus are responsible for spatial specific purposes. orientation. In 2004, they showed that The hippocampus is an older part of the the entorhinal cortex contains an accu- In 2010, it was discovered that rats are cerebral cortex and has a central role rate spatial map of the animal’s environ- born navigators. The brain in newborn in the functioning of human and animal ment. 2005 was marked by the discovery rats comes hard-wired with working memory. The entorhinal cortex contains of grid cells in the entorhinal cortex, navigational neurons. The researchers grid cells, border cells and direction which form a map with coordinates also found grid cells in two new areas of cells that together give the brain the comparable to those on a map you can the brain, outside the entorhinal cortex ability to make highly advanced maps. buy in a bookshop. The following year where grid cells and border cells had been found earlier. NTNU The Norwegian University of Science and Technology (NTNU) is Norway’s primary institution for educating the nation’s future engineers and scientists. The university also has strong programmes in the social sciences, the arts and humanities, teacher education, medicine, architecture and fine art. NTNU’s cross-disciplinary research delivers creative innovations that have far-reaching social and economic impact.

Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory Centre of Excellence Medical-Technical Research Centre, NO-7489 Trondheim, Norway Telephone: +47 73 59 82 42 Telefax: +47 73 59 82 94 E-mail: [email protected] Annual Report for KI/CBM 2011 Annual Report