Edvard I. Moser


Edvard Moser I was born in 1962 on the west coast of Norway, about 200 kilometres north of Bergen. I spent the first 9 months of my life on Haramsøy (Fig. 1), an island with fewer than 500 inhabitants and, at that time, only a single daily ferry connection to the mainland. In 1963 my parents and I moved to a more urban environment, relatively speaking, and settled on another island, in Hareid, a village with about 4,000 inhabitants spread across four different settlements (Fig. 2). My two younger sisters were born there, and I lived there until I finished high school at age 18 in Ulsteinvik, on the same island.

Haramsøy, where I lived the first year of my life.

Figure 1. Haramsøy, where I lived the first year of my life. Taken in 1953, the year when my father moved to the island.

Edvard Moser as a kid.

Figure 2. Me on the island of Hareid in 1963. I lived in Hareid from age 1 to age 19. Photo taken by my father Eduard Paul Moser.

My German Roots

My parents were German immigrants, a rare species in Norway during the first decades after World War II. They met during the war in Kronberg im Taunus, a small village north-west of Frankfurt am Main. My father was the oldest son of the pastor in Kronberg; my mother was the daughter of a famous butcher in Essen, in the Ruhr area near the Dutch border. Together with her siblings, my mother was sent out of Essen when the bombing of the Ruhr area began in 1943. Her father could afford to send his children to a private family in Kronberg through a teacher they knew in the village. The children were brought back to Essen in 1944 because my grandfather feared that Germany would be divided, with Kronberg and Essen going to different territories. After the war, my parents met again in Kronberg and later in Bonn.

Both of my parents wanted an education but did not get an opportunity to pursue one. In my father’s family, the oldest son was expected to be a pastor, which had been the tradition for the last six or seven generations. My father, however, liked to play cello and wanted to study music. After the war there was no money for him to pursue a formal education, so instead he learned a trade in Bonn, with Klais Orgelbau, where he made church organs. After a few years, he came across an advertisement by a small organ factory on an island off the west coast of Norway that was looking for skilled labour. My father applied for the job, got it and moved to Haramsøy in 1953.

My mother wanted to become an interior designer but this type of career was all but closed to her because it required work experience and companies were not willing to accept women for training. Instead she went to a business college and subsequently got a job in Essen as a secretary with AEG, a large German producer of electrical equipment. While she was working at AEG, she came in contact with my father again. He had by then moved to Norway, and my mother visited him on a nice summer day in 1957. In 1958 she gave up her AEG job and moved to Haramsøy.

Norway was a big change for my mother. She came from quite a wealthy family in a big city in Germany. In Haramsøy, she was expected to be a housewife like all other women at the time. The shops had only three types of vegetables – cabbage, turnips and carrots, and there was still outdoor plumbing, which my mother had never experienced before. The weather was harsh and the laundry often flew off the outdoor line where she hung it to dry.

School Days

I was born into two different worlds – a poor community on an isolated but beautiful island that offered little more than was needed for work and survival, and a rich cultural tradition that had its roots in the European continent. A third dimension was added when we moved to Hareid, which in spite of its small size, had an exceptionally active community life centred around the church and the Christian meeting house. But I was still in the middle of the Norwegian Bible Belt – no alcohol, no playing cards, no dancing. My parents’ love for good wines remained a well-kept secret.

I went to primary school in Hareid. As was the practice at that time, all students were taught at the same level, and I had to learn everything at the same pace as everyone else. I was the only child who wanted to learn French, so I was put in a bookkeeping class instead. Occasionally I got a few extra assignments to feed my academic interests, but it was my mother who saved me, by giving me tons of books. I started with Donald Duck comics, which my mother gave me when she wanted me to be quiet during the early morning hours. At the age of 4 or 5, I was so motivated to understand the content of the speech bubbles that I cracked the reading code largely on my own. Later, after I started school at the age of 7, which was when children commonly began school at the time, I got real books – with a strong emphasis on science. I read a lot – about geology, meteorology, palaeontology, astronomy, all of the sciences – and I asked for more. I was totally absorbed by these books.

The books introduced me to science and it became my passion. With a friend I started an astronomy club where we learned everything we could about planetary systems, and we memorised the distances between all of the planets and the Sun (I had an affection for numbers). I bought a globe with the first money I ever earned from mowing the lawn. I learned about all of the countries on that globe, all the capitals, the mountains and rivers, and dreamed about visiting all these places.

My father took me around in Norway in his travels to tune church organs, and we visited remote islands and mountain areas, which fuelled my interest in exploration. I collected stones, I had a herbarium, and I got a chemistry set, which enabled me to create some noxious gases in the bathroom. I played school with my younger sisters – I was the teacher and taught them about everything  I had read. My parents encouraged my interests further by feeding me more books. As I got older, I even sent my mother to the university bookstore in Tübingen to get astrophysics books that I could not buy in Norway.

It became clear to me that someday I might become some sort of scientist, but I didn’t really know what kind, nor did I have any idea about what it really meant to be a scientist. Scientists in the books I read spent their time digging up dinosaurs. During summer holidays in Germany, I visited the Senkenberg Museum in Frankfurt, every time – it was my favourite holiday destination. I saw dinosaurs, fossils, mummies, rock collections, and insects. I wanted to understand evolution and natural history and in my imagination, scientists were people who provided things for the natural history museum.

High school offered me more challenges. The school was in Ulsteinvik, on the same island as Hareid, but on the other side of the mountains. The teachers there were really warm and motivated and suddenly school was much more fun. I was no longer the only one who liked to learn and I could study without disguising it. I liked mathematics and natural sciences but was also fascinated by history and literature, perhaps due to my teachers in these subjects, in particular my form teacher Gunder Runde. With him as a guide, I wrote my thesis about Ibsen. My fascination with Ibsen is still alive to this day. I graduated from high school in 1981 with a top grade in all subjects except physical education (I was never very good at football).

And – I met May-Britt at Ulsteinvik. We were in the same mathematics, physics and chemistry classes, but since she came from another island, and high school cliques were defined by islands, and I was quite shy, we did not interact all that much. When I was not at school and not studying (which I did most of the time), I walked in the mountains on the island. I visited every single peak.

Leaving the Island

I grew up during the Cold War. Military service was compulsory for men who were not absolute pacifists. Most men from my region of Norway were sent to stations in the far north of the country, near the Russian border, and I was no exception. After working for three months at a local shipyard when I had finished high school, I was ready for military service in October 1981. I was trained as a communications officer and worked in an underground bunker in Kautokeino, a Sami village near the border of Northern Finland, in the far north of Norway. I got to know a few people in the village and enjoyed their openness and different life style. I also liked the endless open country, and took long walks when I was not on duty. My task in the bunker was to receive and send secret messages about military activity in the airspace near the Russian border. Not much happened though, so I had time to study differential equations and think about my future.

My year-and-a-half of military service meant that I had to start at the University of Oslo in the middle of the academic calendar, in January 1983. By this point I was still unsure of what I would study but certain that it would be in the sciences. I considered elementary particle physics and nuclear physics but signed up for a course in chemistry. I was fascinated by biochemistry and genetics but had to start with the basics. The first course was in inorganic chemistry. I thought there was too much rote learning and I felt like I wanted to use my energy on other things.

It was about this time that I bumped into May-Britt again by chance. Just before I had moved to Oslo, we met on Karl Johans Gate, Oslo’s main pedestrian zone, and she offered to show me the university. She had been there for a year-and-a-half already and was an obvious guide. It turned out she had also puzzled over studying different science topics – she had taken courses in mathematics, physics and astronomy and was considering a future in geology, since the oil adventure had just started on the Norwegian continental shelf. She even considered becoming a dentist but none of the subjects were as interesting as she thought they would be. So we had something in common (Fig. 3).

May-Britt and me on a tributary of the Amazon in Ecuador in 1986.

Figure 3. May-Britt and me on a tributary of the Amazon in Ecuador in 1986.

Turning to Psychology

At the time I had just finished reading Freud’s The Interpretation of Dreams, and I found it fascinating. May-Britt was also attracted to psychology. In August 1983, we signed up for a one-year bachelor’s programme in psychology. The coursework covered the entire field of psychology, which was much broader than we had imagined. We became aware of behaviourism, which had a scientific rigour that we thought outshined other subfields of psychology. We saw that behaviour could be broken down into elementary laws and that behaviour could be predicted based on the correct timing of discrete stimuli in relation to the animal’s behaviour. At the same time we realised that behaviourist psychology was simple – too simple – and we missed explanations that involved the underlying neural mechanisms.

During our studies, we attended a lecture by Svein Magnussen, in which  he described the pioneering work of David Hubel and Torsten Wiesel, who by the early 1960s had already shown how the visual image was broken down into elementary neural responses in the visual cortex. We went to see our teacher in behaviourism, Carl Erik Grennes, and asked how we could learn more about the interface between psychology and physiology. He gave us a copy of a special issue of Scientific American, published in September 1979, which was all about the brain. The magazine included Eric Kandel‘s demonstration of synaptic mechanisms of memory in Aplysia californica, and the characterisation of the mechanisms for feature analysis in the visual cortex done by David Hubel  and Torstein Wiesel. There was even a piece by Francis Crick, who at the end of his career argued for neural circuit studies and speculated about what was needed for the discipline of neural circuits neuroscience to be born. It was enough to tell us that there was science there to be done.

But in order to get any further, we had to wait a year after our bachelor’s courses before we could start our professional studies in psychology. At that time, psychology was such a popular subject that there was a one-year waiting list, even for those who passed the admission threshold. That year I worked in a psychiatric hospital. I had a full-time job, working with psychotic patients  at an acute ward, before they received medication. In my spare time, I studied mathematics, statistics and programming. I took these courses only because I thought mathematics was fun but it turned out to be very useful for my later work, although I did not realise it at that time. While I was at the psychiatric hospital, May-Britt worked in a geriatric institution while she also took classes. During this waiting period, our interests merged and we started thinking about a common future. We went to Kilimanjaro to get engaged in 1984 and decided to marry in 1985, just before we took up psychology again.

The first semester of the professional studies programme in psychology focused on social psychology. May-Britt and I got involved in a research project on small group dynamics and even contributed to a paper – our first publication. But our interest in the brain persisted and we continued to bug Carl Erik Grenness. Carl Erik advised us to approach Terje Sagvolden, the only psychologist at the university with research projects in neuroscience at that time. Terje was working with neurochemical mechanisms of attention deficit disorder in rats. His idea was that if he found out why a certain strain of rats was hyperactive, that might give us some clues about what causes hyperactivity in children. We learned how to design experiments, we learned behavioural analysis, and we learned more statistics in Terje’s lab. The work resulted in three papers on behaviour in hyperactive rats. The results were perhaps not all that revolutionary but we were proud to see our own work published.

But we were impatient. The focus was still too much on behaviour while the underlying neural operations remained in the dark. Terje saw our willingness to go further and sent us to Uppsala for a collaborative project on neurochemical modulation in hyperactive rats. We stayed for a month but in the end concluded that there was no reason to go all the way around the barn to find the door. In Oslo, there was a famous professor at Terje Sagvolden’s department who was working on the neural mechanisms of memory – Per Andersen. We had seen Per on TV but had never dared to approach him. One day though, after he and his group gave a seminar on the mechanisms of long-term potentiation (LTP) of synaptic transmission and the possible relationship between LTP and memory, we decided that this just might be our future. LTP might be the bridge between physiology and psychology that we had searched for so long.

Working with Per Andersen

One day in 1998, we went to Per’s office and asked if he could take us on as master’s students in preparation for a PhD. Per was quite sceptical. He really didn’t  want new people, because he already had enough students. Moreover, he might not have had the highest opinion of psychologists, although he also wanted to make the connection to behaviour. But we were persistent and shared our ambitions with him. In the end he gave us a paper by Richard Morris, who was at the University of Edinburgh and had invented the water maze, and issued us a challenge: he told us that if we successfully built a water maze laboratory, he would take us on.

A water maze is a big tank, roughly 2 metres across, filled with milky water. There is a platform in the tank that is hidden by the water, which rats can learn to find. As part of our “test,” Per wanted us to actually construct the tank in the basement, but we convinced him that it would be acceptable to buy a tank from a plastic factory on the West Coast that made fish tanks. A few months later the water maze was in place in a small room in the basement. The pool was filled with 1200 litres of water and 3 litres of milk. Every day we emptied the pool, filled again with water, and went to the shop to buy new milk.

We used the water tank to address one of Per’s greatest dreams. He wanted to make an in vivo hippocampal lamella that was as small as possible but at the same time large enough to support learning. The idea was that synaptic changes would be denser in such a preparation – dense enough to be detected by physiological recordings or microscopic analyses. To make this lamella, we removed the remaining hippocampal tissue by aspiration under the microscope. Per wanted the in vivo lamella to be in the dorsal hippocampus but to be sure that the enhanced plasticity of the lamella did not reflect the location of the lamella, we asked Per to include a control group where the lamella was in the ventral part of the hippocampus. We also agreed that we might need to try lesions of different sizes, since we did not know how large the lamella had to be to be functional.

The control group turned out to be the key to our first success in the lab. We found it took only quite small lesions to impair navigation, and we were not able to make the in vivo lamella that Per wanted so much, but there was an interesting dependence on the location of the lesion. The rats with dorsal lesions (ventral remnants) were not able to find the platform but those with ventral lesions (dorsal remnants) could actually navigate very well.

As it became clear that there was a difference between the dorsal and ventral hippocampus in their involvement in water-maze learning, we searched the literature to try to understand it. We came across the work of Menno Witter, who with David Amaral had shown that the dorsal and ventral hippocampus have quite different cortical inputs, and we were able to put the findings into a meaningful context. We wrote up the master’s thesis as a joint thesis of 127 pages and published the results in the Journal of Neuroscience. It was the first behavioural study from Per’s lab and he was probably a bit anxious about publishing it, but after some strong encouragement from several visitors, including Eric Kandel and Larry Squire, we submitted it. It was published in 1993, 3 years after we completed our thesis.

As we finished our master’s thesis in 1990, we both wanted to continue with Per on our PhDs, but the challenge was how to get two fellowships to study with him. At the time it was very difficult to get this kind of funding. There were not many fellowships to hand out and it was not like today, when the labs have the money themselves and get to decide. The Research Council of Norway at the time was concerned about geographic distribution of their fellowships.

My proposed dissertation research was about the relationship between LTP and memory, which was what really got us interested when we first started working with Per, and which had motivated our dorso-ventral hippocampal lesion study. LTP had been discovered 20 years earlier, in Per’s group, and it seemed like the right place to pursue the question.

There were several indications that LTP might be involved in memory, but what Per wanted, and what I also found very interesting, was to see if this phenomenon could be directly observed in vivo. At that time, Carol Barnes had shown that LTP decay correlated with forgetting, Bruce McNaughton had shown that saturation of LTP blocked subsequent memory formation, and Richard Morris had found that learning could not take place if LTP was blocked by an NMDA receptor antagonist. But no one had observed changes in hippocampal excitatory postsynaptic potentials (EPSP) as a direct consequence of learning. So that was the PhD funding I applied for.

At the same time, May-Britt applied for a project where she wanted to see if learning and memory involved changes in the number of synaptic connections, in the same way as seen after induction of LTP. Against all odds, we both did get fellowships.

In 1991, we were ready to learn how to make electrodes and implant them in the brain. We got help with this skill from Bolek Srebro at the University  of Bergen. He showed us how to make electrodes, how to implant them into the hippocampus, and how to read out the field potentials in an awake, freely moving animal. Once I had learned the technique, I implanted chronic electrodes in the performant path and dentate gyrus and let the rats wander around in a box. As they learned about their environment, the EPSPs got stronger, usually for 20–30 minutes. That was by itself no surprise and had been reported previously, but what was strange was what happened when I put the same animals in the water maze. The animals learned to find the platform but the EPSPs got consistently smaller, which really did not make sense. The hypothesis was that they should be larger as a result of naturally occurring LTP.

We finally figured out that the reason for the decrease in EPSPs was that they are very sensitive to the temperature of the brain, so the higher the temperature, the larger the potentials. The water maze was room temperature, much below the body temperature of the rat. I varied the temperature of the water maze and found that the lower the temperature, the more the EPSP was reduced. Per advised me to insert a thermistor in the rat’s brain to monitor the temperature directly and in collaboration with master’s student Iacob Mathisen, I was soon able to show that the strength of the synaptic connection was determined directly by the temperature of the brain. I showed that exploration and other learning behaviours increased brain temperature sometimes by more than 2 degrees and that EPSP changes previously reported to accompany learning were due to temperature, not LTP. We published these findings in Science in 1993. I defended my thesis in 1995, with Bruce McNaughton and Tim Bliss as public examiners, or opponents as they are called in Norway. The thesis defence was part of Per’s ‘Grand Slam’, where 6 of his students publicly defended their work within a week, with an impressive collection of 12 world-leading scientists as thesis opponents (Fig. 4).

Per Andersen and four of the students who participated in his Grand Slam.

Figure 4. Per Andersen and four of the students who participated in his Grand Slam, where six students defended their dissertations during the same week in 1995. Left to right: Mari Trommald, May-Britt, Per, Paola Pedarzani, and me.

I was able to show in my thesis that if temperature was subtracted, there remained small components of EPSP enhancement that reflected behaviour and possibly learning. However, the findings that temperature could so dramatically affect EPSP shook the field. Like several other scientists, when I submitted my PhD thesis in 1995, I was inspired to move on to individual cell recordings, which were much less temperature dependent. This is what finally led me to John O’Keefe’s lab at the University College of London.

Edinburgh Intermezzo

Long before we submitted our theses, May-Britt and I had decided to do our postdocs with Richard Morris at the University of Edinburgh. We met Richard for the first time at the European Neuroscience Meeting in Stockholm in 1990. This was the first time we presented our dorsal-ventral lesion study at a conference and we were extremely proud when Richard referred to our poster in his plenary lecture. Later he invited us to repeat the study with more selective ibotenic acid lesions in his lab, in order to rule out the possibility that behaviour was impaired by dorsal lesions simply because those aspiration lesions severed bypassing fibres. At the same time, ibotenic acid lesions gave us another opportunity to make the in vivo lamella that Per wanted. Perhaps, with more selective lesions, it would be possible to get animals to learn with only a small remaining piece of the hippocampal circuit.

The collaboration between Oslo and Edinburgh started in 1991, when we went to Richard for a month to make the first ibotenic acid lesions. We brought our first daughter Isabel, who was less than a year old, and Richard’s wife Hilary looked after her. We visited several times, and Per visited Edinburgh, and  in 1995 we published the results, showing the same dorso-ventral difference in spatial learning, but now with intact learning even with quite small remnants in the dorsal part of the hippocampus. The remnant was still a lot thicker than Per had hoped for but it showed that hippocampal learning could be maintained with minimal hippocampal circuitry.

Finally, in 1995, after we had submitted our PhD theses in Oslo, we went for a longer visit to Edinburgh. By this time, we had two small girls: Isabel, now 4 years old, and Ailin, who was only 4 months old. Our focus was now on LTP. The aim was to saturate LTP using a protocol developed by Bruce McNaughton and colleagues some years before. Many studies had failed to replicate the learning impairments Bruce and colleagues had demonstrated, but we suspected that the induction of LTP was incomplete and so devised an electrode array that covered a much larger part of the perforant path input to the hippocampus. We struggled a lot to obtain saturation, and I am not sure we ever got it, but at least our induction protocol produced a learning impairment much like that seen in Bruce’s early studies. It took a while to complete this particular project, however. We worked on it in Edinburgh in 1995, then in Oslo during Richard’s winter sabbatical in 1995–96, then in Edinburgh in 1996, and finally in Trondheim in 1996–97, where we got it to work. We did not spend many months in Edinburgh but we learned a lot, met scientists from all over the world, and had great discussions that helped us define and refine our goals. Moreover, I developed a life-long friendship with Richard.

A Quick Visit to London

My postdoc in Edinburgh was paid for by a Human Frontiers grant that Richard Morris had obtained for a group of labs interested in synaptic plasticity. The LTP saturation experiment was part of this project, but based on my experiences from Oslo, I wanted to go ahead with single unit recording and look for changes in neural activity related to memory. I had hoped eventually to set up unit recording in Edinburgh but it was expensive and at that time, the lab had no experience with single units. Richard understandably hesitated but suggested that I instead go work with John O’Keefe at University College London to learn how to do single cell recordings. This suggestion was especially gracious since by this time we were already committed to moving to Trondheim later in 1996. It would also allow us to set up our own single-unit recording lab there.

I have often described the period with John as the most learning-rich time in my life, and it was. John spent an enormous amount of time with me so that I could learn everything about how to make single cell recordings. He showed me how to do the surgery, how to make the electrodes, how to do the recordings, and how to analyse the data. I had a little desk inside his office, which gave me almost unlimited opportunities to ask all the questions I wondered about. In his office, and while I was recording, we discussed what was known and not known about place cells and he alerted me to all the pitfalls in the field – it was all absolutely formative for my future.

I moved to London in March, while May-Britt stayed in Edinburgh to run LTP saturation experiments, but two months later May-Britt came too, as well as our two young daughters, along with May-Britt’s brother and sister-in-law as babysitters. Our visit was a training visit and nothing more but the animals we implanted ran on tracks that could be shortened and extended to dissociate the contributions of landmarks and path integration, a question that we have continued to pursue in our research to this very day. In July, finally, we flew back to Norway, ready to set up our own lab.

The Unexpected Move to Trondheim

Many things happened in parallel in 1995–96. During the course of completing our PhDs and preparing for our postdocs, May-Britt and I were called in for an interview at the university that would become the Norwegian University of Science and Technology (NTNU), in Trondheim, right before Christmas in 1995. Earlier that year, Terje Sagvolden had advised us to apply for a faculty position at NTNU’s Psychology Department and we did so, mostly just to test the waters. We were confident that we would not even be shortlisted, given that we had only a few papers and had not yet defended our PhDs. Yet they were indeed interested and we went to check out the location, even though our plan was to spend at least a few years abroad, in London with John O’Keefe and perhaps later at the Centre for Neural Systems, Memory and Aging in Tucson with our PhD thesis opponents from 1995, Bruce McNaughton and Carol Barnes. At that time, this centre was the mecca for neural population codes for memory.

We told the search committee that we would not be interested in only one position, but Sturla Krekling, the head of the committee, really pushed for us and so they soon offered us two positions. We then said we needed a new lab, and we came to them with a list of all the equipment that such a lab required – right down to the prices and suppliers. We had, after all, been partly through the same process before, both in Oslo and in Edinburgh. They basically gave us everything we asked for and we were offered lab space in an empty bomb shelter in the basement under the department. The only condition was that we begin in August of 1996 so that we could teach.

The request for us to start almost immediately completely upended our plans. But the prospect of two jobs and a lab just seemed too good an opportunity to turn down.

Trondheim – From Bomb Shelter to Lab

May-Britt and I started work in Trondheim on August 1, 1996. We bought a small house near the lab, so that we could run back and forth between the lab and our home to feed the rats and start deprivation at appropriate times, sometimes late in the evening. There were no animal experiments at the department at that time, so we had to build an entire vivarium at the same time as we ordered and set up equipment for place cell recording. We ordered our first recording system from a company associated with the O’Keefe lab – Gignomai, now Axona Ltd – and Jim Donnett and Kate Jeffery came for a few days to help us set up the equipment.

After about a year, we had our first place cell. This was an exciting moment. We brought Sturla Krekling to the lab and he was as proud as we were. With his background from visual-cortex neurophysiology in cats, Sturla was perhaps the only one at the department who really appreciated the spike sounds from the loudspeaker. But the Dean of the Faculty, Jan Morten Dyrstad, a social economist, also showed interest. He was impressed and has since then been one of the strongest supporters of our work. Today he is the chairperson of the Kavli Institute fundraising committee.

It took a long time to collect data because there was only May-Britt and me, and we had to handle routine technical work in addition to the experiments – everything from making cables to cleaning rat cages. In addition, we did most of the teaching in biological psychology, which was quite a lot. The students were excited, and we enjoyed lecturing, but most students were still interested in a clinical career – none of them wanted to spend the rest of their life in a rat laboratory. Thus recruitment was minimal.

In 1999, three years after we started, we managed to attract one student, though. Stig Hollup was different from the other psychology students and liked the technical challenges in our lab. At the same time, we got one part-time technician – Kyrre Haugen, who is still with us. He was able to join our lab because at the end of the year, in 1999, Hans Hellebostad at the Research Council called us and said that they had NOK 100,000 of extra money (about 11,000 euros) that they thought we might be interested in. We were euphoric. Suddenly we had a part-time technician who could section brains and do the histology for us.

But our luck did not end there. At about the same time, the department needed a technician to administer test batteries in the human neuropsychol- ogy section. Luckily for us the HR section misunderstood what a test battery was and recruited an electronics engineer for the job. His name was  Raymond Skjerpeng. He knew nothing about neuropsychological test batteries but was an expert on the type of batteries we used in our lab. Since the neuropsychologists could not use him, we convinced the department to let him join our lab. He was extremely creative and spent day and night in the bomb shelter, helping us build up a state-of-the-art neurophysiology lab.

At the turn of the millennium, May-Britt and I recorded routinely from place cells but the cell yield was quite modest. We knew that to understand memory, we needed simultaneous recordings from large numbers of cells. The place to go to learn large-scale parallel recording at that time was the Barnes-McNaughton lab in Tucson, Arizona, where we had wanted to go as postdocs. In 2001, we were able to take a six-week sabbatical in Tucson where we learned to do parallel recordings from many dozens of cells in the hippocampus. It was a technique that had been developed by Bruce in the 1990s.

The visit in Tucson was another intense learning period. During the day, we wired electrode arrays and used them to record from hippocampus cells while the rats ran on circular tracks. In the evening, we went home with Bruce and Carol, lived in their guest house in the saguaro-studded desert next to the Catalina Mountains, and enjoyed long discussions over a glass of wine in the Jacuzzi in their garden. In the early morning, before it got too hot, we went for a walk in the desert, with their dogs (or half wolves, really) every day. Our two girls went to a Baptist school – the only school that could offer them a place for just 6 weeks. The school was radically different from anything they were used to – the children had to walk in the streets to proclaim the gospel – a different way of expressing religion than what I was used to from the Norwegian west-coast islands – but our two girls learned tolerance and the visit was as formative for them as for us.

During our first years in Trondheim, we were primarily interested in hippocampal mechanisms of memory. We set up a water maze and started recording place cells while rats navigated in a water maze. This was a technically challenging task, as we had to keep water away from the animal’s headstage, but  the electrical silence of the bomb shelter helped, and in 2001 we could report our first findings in The Journal of Neuroscience. We showed that place fields were not evenly distributed in the water maze but were more abundant in the area where the animals found the platform. Many experiments failed though, because water leaked through the insulation around the headstage, so we gradually turned our focus to simpler behavioural paradigms, while at the same time we switched to multi-tetrode parallel recording, based on our experiences from the visit in Tucson.

From Four Hands to Two Dozen

One of the questions that intrigued May-Britt and me most was quite fundamental: What was the origin of the place signal in the hippocampus? With CA1 and CA3 cell recordings up and running in our lab, we saw early on that place cells could be used not only to understand place coding as such but also to more generally understand computation in the hippocampus.

There is no place signal in the sensory inputs to the brain, so how does it come about? Is it generated by the hippocampus itself? Since John O’Keefe discovered place cells in 1971, almost all studies had been performed in the CA1 subfield, the last stage of the hippocampal intrinsic circuit. We wondered if the earlier subfields – the dentate gyrus and CA3 – played any role in the formation of place correlates, and if any part of the signal came from the outside, from the entorhinal cortex, which provides most of the cortical input to the hippocampus.

To address this and related questions we applied for funding from the European Commission’s Framework V programme. This programme funded only collaborative grants. I had never before applied for a consortium, just for May-Britt and myself. To put together an application that succinctly addressed the criteria of the call, we got enormous help from Bruce Reed, a highly intelligent and knowledgeable advisor quite different from any other grant consultant I have worked with. Unlike most of his colleagues, he gave us feedback on the content of our proposal and helped us shape it into an application that pointed directly to the experiments that so tremendously changed our understanding of spatial representation a few years later. In one of the proposal’s work packages, we aimed specifically to determine the nature of the entorhinal inputs to the place cells, in order to find out how they were generated.

The proposal was submitted in 1999, the reviews were positive, and in 2000 I was suddenly the coordinator of a consortium of 7 groups. Among the members in the group were Richard Morris, our postdoc advisor, and Menno Witter at the Free University of Amsterdam, an expert on entorhinal-hippocampal anatomy whom we had already approached in 1990 as we wrote up our master’s thesis on dorso-ventral gradients in hippocampal function. He wrote a long and helpful reply to our letter in 1990, which encouraged us to maintain contact.

The EU grant came at a time when many funding agencies started to get interested in our work. Just a year later, we applied for ‘strategic’ money from the Research Council of Norway. They had a programme to strengthen research in pre-selected areas, and neuroscience was certainly not among those areas. A group of deans at NTNU was responsible for selecting proposals in the right areas. They chose our proposal, despite the fact that it was completely outside of the Research Council’s pre-selected areas. This group included several people who later became rectors of NTNU, including Eivind Hiis Hauge, Torbjørn Digernes and Gunnar Bovim. They all had confidence in our work from the very beginning. I am very grateful for their ability to see the potential in our proposal at a time when we had little published evidence of scientific excellence.

At about the same time, May-Britt and I moved our lab to the Faculty of Medicine. The Psychology Department had given us exceptional start-up conditions, and we are forever grateful to Sturla Krekling, who saw our potential, but psychology is a diverse field, our work was expensive, and we were too different to remain there. To compensate for the lack of biology-minded individuals at the Psychology Department, we had first met regularly with Arne Valberg, a visual neuro-psychophysicist, and Hanna Mustaparta, a biologist who studied neural coding in insect olfactory systems. Based on these encounters, in 2001, after extensive lobbying by Jon Lamvik, a former Dean of Medicine, we were offered lab space at the Medical-Technical Centre, where most of the Faculty of Medicine’s basic experimental research was conducted. The building was immensely crowded at that time, and we are grateful to Jon Lamvik as well as the Dean in 2001, Gunnar Bovim, for making that space available.

As we moved in, our lab was transformed in many ways. Not only did we get an opportunity to build a lab more suited to our increasing interest in the basic computational mechanisms of the hippocampus, but we suddenly had lots of money – from the EU and from the Strategic Research Programme. In 2002, our success continued. The Research Council inaugurated a new funding scheme where 13 Centres, selected among all fields of science and technology, were given extensive funding for 10 years. This was a new funding scheme meant to boost performance among highly selected research groups. We applied for one of these grants. It was a long application process, involving two stages of selection, and our research plans for the next decade were considerably refined as we wrote the application.

A Christmas and New Year’s visit in 2001 by Carol Barnes and Bruce McNaughton helped improve our application. We talked and wrote, went skiing, and celebrated the holidays together. Bruce even dressed up as Santa for the two girls. In the end our proposal was selected, again before we had much of a track record. But I believe the research plans convinced the committee, as well as the proposal to hire 7 internationally recognized scientists as visiting members of the Centre: Carol and Bruce, Richard Morris, Alessandro Treves, Menno Witter, Randolf Menzel and Ole Paulsen.

The idea was that these researchers would visit the lab once or twice per year to participate directly in experiments. So starting in December 2002, the Centre for the Biology of Memory became a reality and all of a sudden we had enough money to address all of our favourite questions. We could buy equipment, we could recruit just the right number of students, and we had some of the world’s best advisors coming periodically to our lab to help us plan and conduct cutting-edge experiments. From late 2002, we were a group with about 10 motivated and talented students and technicians as well as a wonderful international network (Fig. 5).

Our research group in 2002, just after the award of the Centre of Excellence grant.

Figure 5. Our research group in 2002, just after the award of the Centre of Excellence grant. I am in the middle, May-Britt is second from the right.

The Path to the Entorhinal Cortex

The discovery of grid cells began with the study of intrahippocampal origins of the place cell signal. In the 1990s, it was commonly believed that localised firing emerged within the hippocampus, based on weakly spatial inputs from the entorhinal cortex. This belief was based on several studies showing that cells in the entorhinal cortex had large and diffuse firing fields, very different from those in the CA1 of the hippocampus. Spatial selectivity was thus thought to originate somehow and somewhere in the intrahippocampal circuit. To find out how and where, May-Britt and I joined forces with Menno Witter, one of the members of the EU consortium that I coordinated. Along with Vegard Brun, a talented medical student, we selectively lesioned the CA3 of the dorsal hippocampus,  or we used small knife cuts to interrupt connections from CA3 to CA1. With Menno Witter, we used fluorescent tracers to show that after both interventions, intrahippocampal inputs to the CA1 were absent, leaving only the direct connections from the entorhinal cortex.

We expected the lesions to severely disrupt place signals in CA1 but in fact they did not. Despite effective cuts, the cells exhibited localised firing, suggesting that place signals emerged either within the CA1 circuit itself, or were based on spatial signals from the only remaining cortical source – the entorhinal cortex. These findings, published in Science in 2002, suggested it was high time to record within the entorhinal cortex itself – a dormant goal in the EU grant that we wrote in 1999.

Until around 2001, the entorhinal cortex had seemed scary but now we were motivated to get started as soon as possible. We needed students. Vegard Brun was an obvious choice but he had medical exams and was only available parttime so we looked around. A year earlier we had recruited Marianne Fyhn. She applied for a position as a technician but we saw her potential and offered her a fellowship instead. For a while she recorded place cells in the water maze but the task was challenging and we considered alternatives. She was the perfect candidate for entorhinal cortex recordings.

In 2002 we got started. Menno Witter was by now a visiting member of the Centre for the Biology of Memory. Based on his early work on dorso-ventral gradients in entorhinal-hippocampal connectivity, which I had read in the finest detail, and based on the many discussions we had in person as we started our collaboration, it became clear that there was an alternative interpretation to the difference between entorhinal and hippocampal spatial selectivity reported in previous in vivo recording studies. It turned out that these earlier recordings had all been conducted in the intermediate-to-ventral part of the entorhinal cortex, which is primarily connected to the ventral hippocampus, where place fields are large and difficult to identify when rats run in standard-sized laboratory environments.

We  reasoned that it would make much more sense to record in the dorsal part of the entorhinal cortex, from which the dorsal place cells get most of their input. It would also make sense to target the medial part of the entorhinal cortex, considering that much of the visual-somatosensory input reaches this region. Thus, Menno sat down with Marianne and May-Britt and showed them how to access the dorsomedial entorhinal cortex, a chunk of cortex never targeted before in any in vivo study, due to its location at the very back of the rat cerebrum, close to the transverse sinus. It was also not easy to localize in standard atlases of the rat brain, which at time mostly showed coronal and horizontal sections, without a sagittal orientation, which is the only suitable one for localizing electrode traces so far back in the brain.

It did not take long before interesting results surfaced. The recordings showed that entorhinal cells had discrete firing fields much like those of hippocampal place cells but each cell had multiple fields scattered all around in the box. The animal’s location could not be inferred from a single cell alone, but collectively the cells provided a pretty good estimate. It was also clear that the multiple firing fields were not arranged randomly. The distance between neighbouring fields was strikingly constant and clearly different from what could be expected by chance. We published these findings in Science in 2004, knowing now that the dorsomedial entorhinal cortex provided much of the spatial input to CA1 but without being able to understand the neural code of these inputs.

But we were on the right track. At the end of 2004, we presented our findings at the Society for Neuroscience meeting in San Diego. We knew our results contained much of what O’Keefe and colleagues had searched for in their work on the cognitive map and we changed the title of one of our posters to ‘The Entorhinal Cortex as a Cognitive Map’, in order to highlight the connection to John O’Keefe and Lynn Nadel’s work on hippocampal maps more than 25 years earlier. The poster attracted a lot of attention and excitement from the place cell community and from modellers interested in the neural basis of path integration-mediated spatial representation. We got many insightful suggestions during the poster presentation.

One of the most helpful poster session participants was Bill Skaggs, then at the University of California at Davis. After his many useful suggestions on the poster floor, May-Britt and I invited him for a breakfast meeting in order to discuss how such a pattern could arise, in the context of his understanding of continuous attractor mechanisms for place cells, and we discussed ways to follow up on the findings. Bill clearly suggested how hexagonal firing could arise from an attractor mechanism not too different from the ones he had proposed with Bruce McNaughton for place cells and head direction cells. During the course of a few days, it all became clear to us. We  needed to expand the size of the environment, to be sure that the pattern was really hexagonal, the way it appeared to be. We also needed to test animals in darkness, to show that the pattern was path integration-dependent, and we needed to show that the pattern was anchored to visual inputs by testing whether rotation of salient cues also rotated the grid pattern.

Grid Cells

Returning from the Society meeting we had a package of experiments to do, and we again asked Marianne for help, along with her boyfriend Torkel Hafting, who had by then moved to Trondheim. The two of them ran the majority of the experiments, with May-Britt stepping in periodically, working with Marianne in the lab on a daily basis and taking over experiments during weekends or holidays when they were away. My role was to analyse data, write it up, and not least, read, to try to understand. Sturla Molden, the fifth person on the project, wrote code and helped with statistical analysis, including the use of spatial autocor-relation procedures to identify spatial periodicity.

We suspected that there might be something like a hexagonal firing pattern as this was already evident from the recordings in the 2004 paper. However it seemed too good to be true and we needed data from larger environments to be sure that this periodicity was not just coincidental. The turning point was the recording from the circular environment that was two metres in diameter and that we had adopted for this purpose. The arrangement of the firing fields looked strikingly hexagonal – and this became particularly clear when Sturla Molden had finished the autocorrelation program. Within a few weeks, on several occasions, we had multiple Eureka experiences, where it became clearer and clearer that the hexagonal pattern was neither a coincidence nor a technical artefact. The firing fields tiled the entire space available to the rat, in a pattern reminiscent of the holes of a beehive. We had several names for our baby, but because of the grid-like nature of the firing pattern, I suggested we called them grid cells. It was a simple and descriptive term.

The fact that firing fields were so regular despite changes in the animal’s speed and direction suggested that their location was determined by path integration and that grid cells were part of the mechanism for path integration-based spatial mapping – a mechanism envisaged by O’Keefe as early as 1976, but with no evidence for it until now. I was convinced that we had found an important element of the cognitive map – something completely different from anything known elsewhere in the brain. Our journey to this point was aided by important input from the visiting members of the centre. In particular, Bruce McNaughton’s insights in computational neuroscience were really transformative for me. His earlier work on attractor mechanisms inspired me and is still the basis for much of my thinking about how space is represented. With this as a background we felt that we could not only describe a new cell type but we could also put it in a historical and theoretical context. We submitted the paper to Nature, the reviews were positive, and in the summer of 2005 the paper was out.

Finding grid cells was exciting because it gave us another piece in the puzzle of how we navigate in space. But the larger significance of the find is that we were able to see how the brain generates one of its own internal codes, with mechanisms that reflect the inner workings of a cortical system, quite independently of any particular sensory inputs. In the past, it had been difficult to make associations between the firing of neurons deep in the higher parts of the cortex and properties of the external world, because as the distance between the sensory input and the neuron increases, the firing of the neurons is triggered by a multitude of converging sensory channels along with intrinsic processes that we don’t really understand.

But with the grid cells, and the place cells that O’Keefe had discovered, we had neural activity that was clearly associated with a feature of the environment, the animal’s location. Here, we think, lies a key to unlocking the mystery of how the brain computes. There is no grid pattern in the external world so the pattern must originate from activity in the entorhinal cortex itself, or in adjacent structures. Having access to data from these cells felt like a great reward, as it might put us on the track of the more general computational operations of the cortex.

From Lab to Institute

When we found the grid cells, we were still a medium-sized research group, and we had only our own group to care for. But soon after, things started to change. Just before the grid cell results were published, the philanthropist Fred Kavli visited NTNU, along with David Auston, the President of the Kavli Foundation at that time. They were in Norway to prepare for the inauguration of the Kavli Prize, which would be awarded for the first time in 2008. At the same time, they used the opportunity to visit research groups in the fields they were interested in. They came to our lab and were totally struck by the grid cell discovery. At the same time, Eric Kandel, who himself was head of a Kavli Institute at Columbia, argued strongly for a Kavli Institute at NTNU. He was tremendously excited about our work.

Soon after they left, May-Britt and I were invited to submit an application, and in 2007, we became the 15th Kavli Institute in the world and the fourth in neuroscience (Fig. 6). In the end, Fred was enormously proud that a Kavli Institute had been established at his alma mater, although it was important for him, to the very end, that the institute had not been established for that reason but only because it satisfied the foundation’s strict criteria for quality. The inauguration of the institute not only gave us funding and support but also opened doors to some of the best neuroscience groups in the world. Many individuals  made important contributions to the formation of the institute. In Norway, these individuals include two NTNU rectors – first Eivind Hiis Hauge, and then Torbjørn Digernes, who was the rector during the negotiations – as well as the secretary general of the Ministry of Education and Research, Trond Fevolden, and Arvid Hallén, Director of the Research Council of Norway.

In 2007, we became the Kavli Institute for Systems Neuroscience. The picture was taken during Fred Kavli’s visit in 2008.

Figure 6.In 2007, we became the Kavli Institute for Systems Neuroscience. The picture was taken during Fred Kavli’s visit in 2008. Left to right: me, Fred, May-Britt and Menno Witter.

The establishment of the Kavli Institute represented the beginning of a transition from a single-group centre to an institute. Menno Witter was the first new faculty to join us. Menno had collaborated with us almost from the beginning, when we got our first EU grant in 1999. He became a member of the Centre for the Biology of Memory and participated in some of the most important studies in the Centre’s history – studies that led up to the grid cell discovery and several studies that investigated their properties. In 2007, with the Kavli Institute in place, and with the help of the Dean of the Faculty of Medicine, Stig Slørdahl, we were able to offer Menno conditions that convinced him to move his entire research group to NTNU.

A few years later, in 2010, we recruited Yasser Roudi, a theoretical and computational neuroscientist, and a student of Alessandro Treves, who is a visiting member of our institute. In 2013, Cliff Kentros moved from the University of Oregon to set up a group for studies of memory using transgenic mouse technology, and in 2014 we recruited Emre Yaksi to set up a lab for zebrafish studies of the nervous system. Jonathan Whitlock joined the faculty when he received a Starting Grant from the European Research Council.

The Connection to Memory

The discovery of grid cells opened the door on understanding the brain’s system for spatial mapping. However, the brain regions containing place cells and grid cells are also crucial for everyday memory and it was the relation to memory that motivated our first studies in the hippocampus. What could be the link between space and memory? Are the same neurons involved and if so, how can they perform both functions? To understand this relationship, May-Britt and I maintained our interest in memory and conducted a number of studies, in parallel with the entorhinal work, which made it easier to understand how the two phenomena are related.

By 2002, when we moved out of the Psychology Department, we had realized that place cell recording in the water maze was too ambitious. The problem was not primarily the contact with water but rather the complexity of the task. Recording while rats learned to find the hidden platform might reveal activity specifically related to storage of spatial information but the task could be solved in many ways, and it was difficult to rule out the contribution of trivial sensory or motor contributions to changes in firing rates. Thus we were increasingly attracted to simple reductionistic paradigms such as the old open field that we started out with during our work on hyperactive rats with Terje Sagvolden. After a few years in the new lab at the Faculty of Medicine, we made sure that all the rooms in the lab had open fields.

So how could we address spatial memory in an environment with no goal to search for? In the late 1980s, Bob Muller and John Kubie at SUNY Downstate had shown that place cells ‘remap’ between environments. They trained animals in different versions of the same enclosure, in the same place, and found that each enclosure was associated with a different subset of active cells. Along with later work from a number of laboratories, including that of Bruce McNaughton and Carol Barnes in Tucson, they showed that hippocampal ensembles switched between quite different firing patterns as animals moved from one environment to another, and sometimes even when only task factors were changed within the same environment.

It became clear to them, and to us, that remapping might serve as a window on the mechanisms underlying memory storage in the hippocampus. Each environment had its distinct representation, mediated by different combinations of active cells. It seemed like the hippocampus had one map for each environment, operating much like a catalogue for all environments that the animal had encountered. Studying how these representations are formed and how they are segregated from one another felt like an interesting set of questions to pursue.

For our studies of remapping, May-Britt and I recruited Stefan Leutgeb, one of the postdocs who participated in our first EU grant. Stefan shared our interest in neural substrates of memory, as well as computational differences between the hippocampal subfields. We started out by comparing CA3 and CA1 and found, in collaboration with Alessandro Treves, a visiting member of the Centre, that place representations in CA3 cells were much more decorrelated than those typically recorded in CA1. Later work, with Jill Leutgeb, who joined the lab a year later, as well as with Bruce McNaughton and Carol Barnes, showed that CA3 networks had attractor properties, although transitions between representations were not always as sharp as envisaged if the hippocampus contained only discrete attractors.

Our work showed that there are two types of remapping – sharp transitions similar to those seen by Muller and Kubie, which we referred to as global remapping – and more gradual transitions, in which firing rates changed smoothly as external inputs were altered, whereas firing locations remained the same. The latter was dubbed rate remapping. The studies of remapping were possible because we could record large numbers of cells at the same time, using the multitetrode technology that we had learned from Bruce and Carol during our 2001 visit in Tucson.

The use of remapping as a way to understand hippocampal memory begged an obvious question: how was hippocampal memory, expressed through remapping, influenced by inputs from grid cells in the entorhinal cortex? Grid cells are the most abundant cell type in layer II of the entorhinal cortex, and it was very likely, as shown in more recent work from our lab, that they provide a significant share of the projections from the medial entorhinal cortex to the hippocampus.

This led us to compare representations across environments in grid cells, at the same time as cells were recorded in the hippocampus. Again with Marianne Fyhn in the lab, we recorded grid cells and place cells in different enclosures  in the same place or in different enclosures in different rooms. With the help of Alessandro Treves, we cross-correlated ensemble maps from each environment to see if relative firing locations and orientations were maintained. The striking finding was that the map structure was maintained in grid cells whereas no similarity was preserved in the hippocampus, suggesting that as information is passed from grid cells to place cells, it is completely transformed – from a single universal map in the entorhinal cortex to a multitude of almost-orthogonal maps in the hippocampus, with apparently one map for each environment.

In this sense, the grid cell map was similar to maps of head direction cells in other areas, which also maintained their intrinsic structure across environments. The data suggested there were two types of spatial maps – a rigid map in the entorhinal cortex that maintained a single metric independent of the nature of the environment, and a much richer map in the hippocampus with representations individualised to each environment, much as one would like for a memory storage system. The relationship between the two maps intrigued us, and with Laura Colgin, we showed that spatial maps in the entorhinal cortex and CA1 are temporarily synchronised via oscillations in the fast gamma range. Between these short moments of entorhinal-CA1 synchronisation, CA1 cells synchronise with CA3 cells possibly involved in the internal storage of spatial representations. Finally, using new molecular and optogenetic tools, we also showed, with Sheng-Jia Zhang and Jing Ye, that grid cells project directly to the hippocampus, as hypothesised by our work on remapping. Thus, by approximately 2012, we felt that we had an improved understanding of how grid and place cells interact, although there remain major questions yet to be answered.

Grid Cells: From Single Cells to Networks

The discovery of grid cells also led us to ask what the intrinsic network of the entorhinal cortex is like. How is the grid pattern formed? How do grid cells interact; what can they achieve together that they cannot do alone? What other cell types are there and how do they all interact?

Since the discovery of grid cells, my fascination with their crystal-like firing pattern and its potential mechanisms has not flagged. In 2005, we were able to record only a few grid cells at the time and it was difficult to infer how they operated at the ensemble level. This has changed. In 2009, Hanne and Tor Stensola, another couple, joined our lab. Hanne had a talent for recording large numbers of grid cells in the same animal and Tor a talent for devising clever analyses to infer their systems properties. They were able to record almost 200 grid cells per animal, enough to demonstrate that grid cells are organised into a small number of functional modules, each with its own unique grid spacing. This result was published in Nature in 2012. We found that modules can operate independently in the presence of changes to the geometry of the environment.

Two years later, during the Nobel celebrations in Stockholm, Nature accepted a second major finding from their work. We were able to show that  grid cells align with borders of the local environment through a shearing-like mechanism that causes both deformation and rotation of the grid pattern. The asymmetry of grid cells is completely predictable by the shearing mechanism that we described.

But what was behind the mechanism of the grid pattern? Early on, Bruce McNaughton alerted us to the significance of attractor network mechanisms  in spatial representation. Our interest in these kinds of representations grew as Yasser Roudi joined the faculty to start a theoretical physics group. Shortly after Yasser moved to Trondheim in 2010, Menno Witter’s group had shown that stellate cells – most of which are likely to be grid cells – lacked excitatory recurrent connections. The lack of such connections was a puzzle for attractor theories of grid cells but Yasser and his colleagues showed that hexagonal symmetries could also be obtained by purely inhibitory interconnections.

The attractor model explained some key features of the data. The observed independence of the grid modules, for example, was exactly as predicted. For grid patterns to appear as an equilibrium state in a network of interconnected neurons, and for such patterns to be updated in accordance with the animal’s movement, interconnected cells may need to share both grid spacing and grid orientation. This means that the network must be organised in a modular fashion, with each module corresponding to a semi-independent attractor network. The data have convinced me that grid cells do, to some extent, reflect attractor mechanisms but the detailed implementation of the mechanism is clearly not well understood. Digging deeper into the mechanism of the grid pattern will certainly be among our major goals in the years to come.

Grid cells do not operate in isolation, however. Soon after the discovery of grid cells in 2005, Francesca Sargolini came to the lab. She showed that there are head direction cells in the medial entorhinal cortex, especially in the deeper and intermediate layers, and that they intermingle with grid cells in these layers. Head direction cells are cells that fire selectively when animals face a certain direction, with activity similar to a compass, except that the firing direction is determined by local cues, not magnetic inputs. Head direction cells were discovered by Jim Ranck at SUNY Downstate in 1985, in the dorsal presubiculum, adjacent to the medial entorhinal cortex, but Francesca’s head direction cells were the first in the entorhinal cortex. Many head direction cells were grid cells at the same time. We called them conjunctive cells. The combined spatial and directional signal of these cells obviously pointed to a close link between the metrics for direction and location.

The search for additional cell types also led us to discover border cells in the entorhinal cortex. With Trygve Solstad and others in our lab, we found that approximately one-tenth of our cells fired selectively along walls or edges of the recording environment. They did so in every single environment, and their firing also lined up along small wall inserts within an open field. Border cells were functionally different from their more abundant counterparts, the grid cells. Entorhinal border cells were also observed by Jim Knierim’s group, then at the University of Texas in Houston, and cells with similar properties, referred to as boundary vector cells, had been reported by John O’Keefe and colleagues in the subiculum. The entorhinal border cells were intermingled with head direction cells and grid cells, and they were also present in layer II.

Finally, quite recently, we have shown that grid cells, border cells, and head direction cells co-localise with speed cells, cells that fire linearly in relation to the animal’s instantaneous speed. This is work we have conducted with Emilio Kropff, who worked as a postdoc in our lab. Combined, these many cell types form a network of diverse cells with distinct functions, all embedded in the same network. Understanding how this network of cell types operates to form a holistic representation of space will keep us busy for many years to come.

The Next Decade

After the 10-year lifetime of the Centre for the Biology of Memory ended in 2012, we were awarded another decade of funding. The Centre for Neural Computation, with May-Britt as the Director, will be alive until 2023 and we expect the number of faculty at this centre to increase. The rapid expansion of our activity is the result of generous support from Stig Slørdahl, the Dean of the Faculty of Medicine, who has used every opportunity to help us to further improve and extend the centre. At the same time, the Research Council and NTNU have given us funding for an almost ten-fold expansion of the lab space of the institute, and the Ministry, in collaboration with the Research Council, gave us more or less permanent support for technical and administrative staff – support that is generally not easy to obtain through regular grants. Because of this support, the team has been transformed from a single entity with a strong focus on a single cluster of questions to an entire institute consisting of multiple research groups covering a broad range of systems questions, well beyond the domain of space and memory.

With the new centre funding, we are also establishing new collaborations. One of these is with Tobias Bonhoeffer from the Max Planck Institute for Neurobiology outside Munich. He joined us as a visiting professor in 2014 and works with us on using two-photon imaging to establish the detailed functional organisation of the grid cell network. A student of ours, Albert Tsao, has been working in his lab for almost two years and I have visited Tobias’ lab frequently. At the same time we are setting up imaging technology in our own lab. The collaboration re-establishes a friendship that started almost 50 years ago, when the two of us used to play in a sandbox in a residential area in Tübingen in Germany. I used to spend parts of the summer with my parents visiting my aunt and uncle, Ulrike and Hermann Lange, who lived just a few houses away from the Bonhoeffer house. We rediscovered our friendship when Tobias’s mother told him about the Norwegian boy who came to visit every summer. Today Tobias is the external collaborator who is most strongly transforming our lab, via his help to introduce imaging technology for population studies of grid cell activity. He is not the only one, however. Pico Caroni is also a very valuable member, as is John O’Keefe, who is, and always has been, a thoughtful and forward-looking discussion partner.

The Call from Stockholm

On October 6, 2014, I was on the plane to Munich for an extended research visit to Tobias Bonhoeffer’s group at the Max Planck Institute for Neurobiology near Munich. While I was in the air, working on a manuscript, my life changed dramatically, without me knowing. My first surprise was the encounter with a representative from the Munich Airport who met me with flowers and an airport car at the gate when we landed. She told me I had won a prize but mixed up things and said it was a prize from the Max Planck Society.

The text message from Göran Hansson, the secretary of the Nobel Committee.

Figure 7. The text message from Göran Hansson, the secretary of the Nobel Committee, which I received when I landed at Munich airport on October 6, 2014. English translation: “Edvard, call me as soon as possible. Important!”

It was only when I checked my  iPhone that I started to understand (Fig.  7). There was a text message from Göran Hansson, the secretary of the Nobel Committee, as well as hundreds of other emails and text messages. Then Tobias called and congratulated me. A few minutes later I was met by Tobias and his lab, with champagne in the arrivals hall, and an hour later there was a press conference and even more champagne. After an hour or so was I able to connect with May-Britt, who got the call from Göran Hansson two hours before I became aware of the news from Stockholm. On the day after, on October 7, I was back in Trondheim, to celebrate the event with the family, the lab and the rest of the university (Fig. 8).

Welcome at the Trondheim airport.

Figure 8. Welcome at the Trondheim airport upon my return on October 7.

The subsequent weeks were crazy. It took a while to get organised and find a way to handle the steady flow of requests to lecture, open conferences, and give interviews and comments. In the end I learned to prioritise and life got back  to normal, with the brain at the centre. Then, in December, the celebrations started again. The Swedes treated us like kings. Each laureate had his or her own attaché who took care of all appointments and guided us from event to event. The ceremony was moving. Receiving the medal from King Carl Gustaf on the stage, with applause from a packed audience, is imprinted in my memory, as is the Nobel lecture in the new Aula Medica, in front of 1,200 attentive listeners.

It was delightful to share the experience with John, our generous mentor from the 1990s and such a thoughtful scientist. I liked the other laureates. By the end of the Nobel week, we felt we knew all of them a little bit. And I must add that the Swedes really know how to celebrate science. Torsten Wiesel and Eric Kandel had come to celebrate with us, as had numerous colleagues and collaborators. When we left on December 13, I believe everyone in the country knew what a grid cell was. Our research had reached the public and I got the impression that they all celebrated with us. It was a prize not only for systems neuroscience but also for research in Norway and Scandinavia, and everyone was part of it.


My journey from Haramsøya – that small island off the coast where I was born – to Stockholm has been quite an adventure. Who would have predicted this when I entered the world from our modest house on that little windy island of farmers and fishermen? I am still not entirely certain what made it possible. The academic interests of my parents certainly contributed, but in the absence of an external intellectual environment, and with no extra stimulation in primary school or secondary school, the fact that I became a successful scientist was perhaps somewhat against the odds.

Even after I knew that I wanted to spend my life doing research, success was far from guaranteed. Finding the right research group is an essential part of any science career, and I can say that my choices were fortuitous. I learned behavioural analysis with Terje Sagvolden but switched to neuroscience with Per Andersen at the right time, when we – and the field – were ready to bring psychology and physiology together.

Since our PhD days, May-Britt and I have been helped by individuals and institutions, all of whom saw the potential in our work and supported us. Perhaps my personality also helped a little bit. I have a strong will and can be extremely focused on a particular goal, even if it is decades away. My slight enthusiasm for mathematics has been useful, as well as my passion for putting together disparate pieces of information. With the help of May-Britt I felt I could sometimes see the whole picture and the path forward. However, it remains for the historians to put it all together.

Let me finally add that my scientific journey did not happen in a vacuum.  I have had a wonderful partner and we in turn have two remarkable daughters – Isabel and Ailin. They were born in 1991 and 1995, respectively, and came with us as we travelled the world – to Edinburgh where we worked with Richard Morris, to John O’Keefe in London, and to Bruce McNaughton and Carol Barnes in Tucson. Together we have explored the planet, not only laboratories and conference auditoriums, but also beaches, rainforests, volcanoes, reefs and remote islands. Today our two girls are mature, thoughtful and warm young women who continue to bring happiness to my life (Fig. 9). That is a gift that is even greater than the Nobel Prize.

Daughters Isabel and Ailin.

Figure 8. My daughters Isabel and Ailin from a tour in France in 2012.

From The Nobel Prizes 2014. Published on behalf of The Nobel Foundation by Science History Publications/USA, division Watson Publishing International LLC, Sagamore Beach, 2015

This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/ Nobel Lectures/The Nobel Prizes. The information is sometimes updated with an addendum submitted by the Laureate.

Copyright © The Nobel Foundation 2014

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