Advancing Basic Science for Humanity
At the Centre of It All
Kavli Institute Directors Edvard and May-Britt Moser have just established the Norwegian Brain Centre at NTNU. With the opening, the Centre becomes one of the largest of its kind worldwide, and the Kavli Institute is at its core.
Edvard and May-Britt Moser, Co-Directors, the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology in Trondheim.
EDVARD AND MAY-BRITT MOSER are world renowned for their discovery of a grid cell network in the brain of the rat that, like a GPS system, maps the animal’s place in space. These specialized neurons with evenly spaced firing locations aid the animal’s navigation, also known as “dead reckoning,” and help explain how rats can find their way even in the dark.
Husband and wife, the Mosers have conducted all their research together since meeting as undergraduates, and currently co-direct the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology in Trondheim. This Institute was recently joined by a new Norwegian Brain Centre at Trondheim, which the Mosers established after receiving a 5.6 million euros grant from the Norwegian Research Council. The Centre will be one of the largest of its kind worldwide.
After the Centre officially opened February 28th of 2012, the Mosers spoke to The Kavli Foundation about how the new facility will greatly expand their research capabilities, foster more training and research collaborations, and help them and others make the leap from animal to human studies of spatial navigation and memory. Below is the condensed and edited transcript of that conversation.
THE KAVLI FOUNDATION (TKF): To begin, can you tell us how the new brain research center will interact with the Kavli Institute for Systems Neuroscience and expand its capabilities?
EDVARD MOSER: The Norwegian Brain Center will be the umbrella organization that will include the Kavli Institute as its core, in which most of the research activity will still take place. But the center will also offer training and research space to other visiting researchers, who will come for short-term or more permanent stays. These investigators will come from other labs in Norway or from abroad in order to learn our experimental methods and techniques, and to do experiments that only can be done with the type of equipment we have. There have been a lot of requests for this training, but before we got the Brain Centre, we didn’t have the space or equipment to provide it. With funding for training and for much larger labs and extensive equipment, we will be able to reach out to more people in the research community, which we hope will foster more research collaborations. With well over 4,000 square meters of research space, our facilities are almost ten times larger than they were.
A Ten-Year Chronology
There has been a fruitful relationship between the resources the Mosers have received over the past decade and the pioneering research findings they have made in the area of spatial navigation and memory, as is revealed in this timetable dating from 2002-2012. Click here.
TKF: So by how much will the Centre increase the number of neuroscience research labs at Trondheim and what will those be focusing on?
EDVARD MOSER: There probably will be 5 or 6 other neuroscience labs in addition to the ones inside the Kavli Institute. Currently, in addition to the basic research that is taking place at the Kavli Institute, there are studies of rats genetically engineered to have a human gene known for fostering susceptibility to Alzheimer’s disease, to see how that gene affects the part of the brain where the grid cell network is located. Within the Kavli Institute, we also have a new group in computational neuroscience that is doing computer modeling of the grid cell network and showing how the cells work together and with cells in other parts of the brain. Another new group will focus on the molecular biology of that network. These groups will in turn interact with the larger neuroscience community, including those who use functional imaging methods to study the brain in memory tasks.
TKF: How will the computer modeling help your research?
On February 28 the Norwegian Prime Minister; Jens Stoltenberg, officially opened The Norwegian Brain Centre at Norwegian University of Science and Technology (NTNU). Instead of cutting a ribbon, the Prime Minister connected two cables that illuminated a blue light under the centre's unique cornerstone, which is crystal and contains a reconstruction of a stellate cell of the rat’s entorhinal cortex, which has helped the NTNU researchers unlock the secrets of spatial map formation in the brain. (Courtesy: NTNU)
EDVARD MOSER: The grid system is so complex—in the rat brain there are probably over 100,000 cells that comprise it and several different cell types. So it’s hard to imagine how the cells all work together. It’s been extremely rewarding for us to have the computational group that builds these models and tests them in computer simulations to see what is possible, and generates new ideas that we can then test out in experiments.
MAY-BRITT MOSER: It’s really exciting—we have two papers we recently submitted to a high-profile journal that use the same model. In one, the model is developed from cell data, and in the other paper we share our results of testing the model in rats. Both show how grid networks emerge—the mechanism that generates them.
TKF: What new equipment will you be getting?
EDVARD MOSER: We will invest in a broad range of state-of-the-art neuroscience equipment – everything that is needed to perform multi-level integrated systems neuroscience with the most recently available methods. We will be getting more neurophysiological equipment—systems that allow us to record the electrical activity simultaneously from many cells in the brain so we can start to understand how they work together to form a spatial map in your mind and help you find your way. Before the grant, researchers would have to share the same equipment so they couldn’t continuously do experiments using it.
MAY-BRITT MOSER: For example, there were researchers trying to study the development of grid networks in the young rat. These scientists could only do recordings every other day because they had to take turns with other researchers to use the same equipment. This was a major problem for development studies because of all the gaps in data collection.
"The Norwegian Brain Centre will include approaches that will take steps toward clinical applications, whereas the focus of the Kavli Institute within it will always be basic research. That’s our mission—we want to understand how the brain works. But we also want to communicate that to people who can use it to understand diseases." — Edvard Moser
EDVARD MOSER: We will also be getting more microscopes and connectivity of neurons in the brain will be studied using new transgenic methods. There’s a desperate need to know how all the cells in the grid network are wired together and the microscopes will help with that. They will also enable us to put a lot of electrodes in the same part of the brain at the same time. That way, we can record simultaneously from many different cells and find out a lot about connectivity. We will also have a lot of improved optical and genetic engineering equipment that will allow us to increase or decrease the activity of specific populations of brain cells in living animals by just shining light on them or by giving the animals a certain drug. That way we can target widely distributed cell types and see what roles they play in spatial navigation in vivo.
TKF: It sounds like now that you’ve figured out the different components of the grid cell network, you are trying to figure out how they all work together.
EDVARD MOSER: Exactly. What we have been studying is how do we get a map of space in our brains, but the next question of course is how do we use this map to get from point A to point B. That’s something we really don’t know much about yet.
TKF: So what specific questions do you hope to answer with your research?
As rats explore an environment, neurons called grid cells fire in a regular geometric pattern, as indicated in this image. This firing enables the animal to determine where exactly it is located and aids its navigation. (Credit: Lisa Giocomo, KISN)
EDVARD MOSER: How do the different cell types in the grid network – the grid cells themselves, the direction cells, and the border cells – both help you to form an instantaneous idea about where you are and store memory for all the different environments you’ve experienced? How are all of these memories of places filed away separately in your brain? These are just a few of the questions we’d like to answer.
MAY-BRITT MOSER: We also want to study how we can manipulate the grid cell network during development. Are we born with a perfect spatial navigation system, or does the environment you are exposed to make it better or worse?
TKF: But so far we don’t know if people have the same grid cell networks that rats do, right?
EDVARD MOSER: Yes and no. Some Israeli scientists recently reported that they had found these networks in bats that are on a completely separate branch of the evolutionary tree than rats. This finding makes it very likely that the grid cells arose early on in evolution and became a part of the brains of all mammals, including humans. The reason we are working on rats is because if you are looking for general principles, it’s almost always the same across mammals. It’s like DNA—it’s not reinvented just for humans.
MAY-BRITT MOSER: We also hope to start a research project in collaboration with the clinicians to figure out if humans also have the same grid network for spatial navigation and if humans use it in the same way as the rats. That’s one of the things our new Norwegian Brain Research Centre is enabling—collaborations between researchers at the nearby Saint Olavs Hospital and our grid network researchers.
TKF: So the Centre is letting you venture into the arena of human research?
MAY-BRITT MOSER: We would love to see that happening. For example, we have a group of clinicians here at the hospital doing deep brain stimulation in Parkinson’s patients, which involves inserting deep within the brain devices that provide electrical stimulation, with the hope that it will replace the electrical stimulation needed for movement that is lacking in these patients. If they can record nerve cell firing from these and other neurosurgery patients, then we may perhaps learn about the functions of the human grid network. The people at the hospital are really eager to get this going so hopefully it will happen. We also plan to get clinical researchers from abroad to work as visiting professors to guide us because we don’t know much about humans. And we want to train medical students on how to do good science on rats, so these students can use those skills and scientific ways of thinking when they start working with patients.
EDVARD MOSER: The Norwegian Brain Centre will include approaches that will take steps toward clinical applications, whereas the focus of the Kavli Institute within it will always be basic research. That’s our mission—we want to understand how the brain works. But we also want to communicate that to people who can use it to understand diseases.
MAY-BRITT MOSER: You have to understand how the normal brain works in order to understand what goes wrong in brain diseases.
TKF: Do you think the grid-like encoding that you have uncovered for spatial memories could also encode other types of memories?
EDVARD MOSER: Every memory of daily experiences is plotted on top of a spatial map so whenever you recall an experience—what you had for breakfast today, for example—it is always in a spatial context. When you record that memory, you also record the place where it happened. The output from the grid cells is a kind of matrix or coordinate system on top of which you recall all kinds of other things, which are recorded in the hippocampus.
MAY-BRITT MOSER: A good example of how you use space to help memory retrieval is you may be in your kitchen when you realized you needed something from the basement. But when you get to the basement you forget what you came for. Most of us in that situation would then go back to the kitchen to remember the item we had forgotten.
TKF: Do you think a faulty grid cell network could explain why I have no sense of direction?
EDVARD MOSER: We get asked that question all the time. People have different navigation abilities and these relate to some extent to training, but there is probably also a strong genetic component. The grid cells we are working on are required for such basic functions as just finding your way from the desk to the door—it’s something that everyone uses. But problems come when there are many million landmarks to keep track of or when landmarks are few or ambiguous and you need to rely on the brain’s spatial metrics, i.e. the grid-cell system. However, accurate navigation depends not just on adequate grid cells but also on adequate memory and attention. Quite often, people who say they don’t find their way partly cannot do so because they don’t pay attention to their surroundings. Like when I am engaged in conversation while following someone around in a new city, and I find myself totally lost afterwards.
TKF: These days you don’t have to rely on these capabilities and can rely on a GPS system instead.
MAY-BRITT MOSER: We don’t think so because we had a really bad experience with a GPS system. We were driving to the SUNY Downstate Medical Center in Brooklyn, New York, from Washington D.C. so we could give a seminar about grid cell networks. We used a GPS system to guide us, but somehow it reset itself before we got there and made us go back in the direction from where we came. It wasn’t until Edvard noticed that we were driving on the bridge back to Staten Island, which we drove on previously, that we realized the GPS wasn’t working properly. The GPS system fooled us and the end result was that these people were waiting for more than half an hour for our talk about spatial navigation!
- May, 2012