Neuroscience

How the brain creates memory

By Ragnhild Krogvig Karlsen
January 29th 2007

Imagine coming up from an unfamiliar subway station. You immediately look for a landmark to figure out where you are and how to get where you want to go. The moment you find it, your cognitive map is calibrated, and things fall into place,” explain Edvard and May-Britt Moser. They are solving the mysteries of memory.|

Illustrasjonsbilde/FOTO
Introduction
The Centre for the Biology of Memory (CBM) is one of the leading research environments in the world on knowledge about memory.

They develop and combine new tools and methods, and by doing so they have built a laboratory that in recent years has presented ground-breaking results. In 2005, they discovered the grid cells that have a key function in the brain’s work of providing us with a sense of locality. This locality centre of the brain is at the same time deeply involved with the biological processes creating other types of memory. Through both theoretical and experimental research, CBM continues the work of understanding the mechanisms of coding, storing, intensifying, and recalling memories in the brain.

They study the functions of the individual cells as well as how the network of neurons cooperates in and across different areas in the brain. In the longer term, this will provide basic understanding enabling the development of treatment for severe diseases affecting memory, such as Alzheimer’s disease.

Illustrasjonsbilde/FOTO Discovered the sense of locality
In 2005, CBM discovered the central of the brain’s spatial computer. The discovery of the grid cells governing the sense of locality was so sensational that the journal Nature printed a feature story about it. For 30 years, brain researchers have known that certain cells in the hippocampus – the part of the brain important for storing everyday memories – are activated when we are in a particular place.

But the ‘spatial computer’ or coordinate network CBM has discovered lies in a totally different part of the brain called the entorhinal cortex. This part of the brain operates in interaction with the hippocampus. “This network of cells functions as a communication centre between the hippocampus and the rest of the cortex,” said Professor Edvard Moser.

Different types of memory
Adults also have newborn brain cells, but their function is one of the mysteries Professor Moser wants to solve. The brain is never full. It stores impressive amounts of information. The more we associate with a memory, the easier it is to recollect. Within three seconds you can recognize a face you thought you had forgotten.

At the same time it is fascinatingly strange how difficult it can be to remember certain things when you need them. In 2004, Edvard and May-Britt Moser presented some explanations to this fact in Science. Different types of memory, such as recognition and recalling are processes that use different networks in the brain. When you memorize names on a guest list and somebody asks you afterwards if John was among the guests, you use recognition.

In that case, it is sufficient that the signals are sent in a direct line between the hippocampus and the cortex. In the case of recalling, on the other hand, the route is more complex. If somebody asked you to remember all the names on the guest list, a closely integrated network of signals in the hippocampus is activated.

The brain stores and uses pegs
When we remember events, the memories are almost inextricably connected to the place where it happened. We create pegs where the memories are attached. When neurons create connections in this way, the brain creates associative memory, a field also being researched at CBM. The memory processes do not take place in single cells, but in dynamic cell networks.

Illustrasjonsbilde/FOTO Rat race in the laboratory
CBM combines behavioural research and physiological experiments. The studies and measurements are performed on rats. In the laboratories, tiny sensors with a diameter of 1/3 of a strand of hair are attached to single cells in the brain via a permanent implant on the rat’s head. Then, the rat runs around finding its way through small, purpose-built rooms with different shapes.

They are tested in circular rooms, square rooms, on straight courses and in labyrinths, in light and darkness, and in the passage from one type of room to another. There is no doubt that the rats are having a good time in these situations, while the researchers digitally register the cell activities. This is playing and looking for goodies for both parties.

That is how CBM discovered the ’spatial computer’ – the continually updating cognitive map. The signals drew a checker-worked print of the area the rats were moving in. ”No matter where the rats went, their brains made this checker work – even when the rats moved in darkness,” Moser said.

Obstacle race with animals
CBM emphasizes ethics and follows Norwegian and European ethical guidelines for animal protection. According to these guidelines, animal experiments are to be conducted using the lowest possible animals. At the same time, rats are interesting experimental animals because they are intelligent. Compared with mice scurrying off, rats are better suited for brain activity measurements since they stop, reflect, and process impressions as they go. They are easy to study due to their temperament as well as their behaviour.

Reliable and relevant measurements also depend on the experimental animals being in a harmonic and relaxed condition. For this reason they are treated as pets. The researchers have individual responsibility and operate implants on their own rats. On the inside, the rat brain is surprisingly similar to the human brain. When the experiments deal with such basic physiological level as networks of neurons and single-cell measurements, the results can be transferred to mammalian brains in general.

Illustrasjonsbilde/FOTO Brain sections – Hippocampus does not operate alone
The histology laboratory is the next station for the researchers – and sadly the terminal for the rats. Here, sections of the rat brains are prepared. They are placed under the microscope and function as frozen snapshots of what has happened in the brain at certain moments, and in the learning process during the experiments. The hippocampus is the part of the brain that has been researched the most, and one look into the microscope reveals the reason why. The hippocampus is found on each side of the brain like two thin sausages – or seahorse tails – in rats they are the size of cashew nuts. They stand out with a distinct profile because the area is packet with neurons and nerve fibres.

Success – attracting international resources
In 2005, at the Society for Neuroscience’s meeting in Washington gathering of 35 000 scientists, two lecturers attracted an audience of more than 6000. They were the Dalai Lama – and Edvard Moser.

”We are currently experiencing a wave of students and researchers from all over the world wanting to come to the Centre. IWe need to take very good care of this positive reputation," said May-Britt Moser with a smile – knowing that CBM quite literary have triggered a scientific rat race. Research groups all over the world are joining the race towards the next milestone.

In 2008, CBM is arranging a world conference at Svalbard with leading researchers in neuroscience, and promises a happening nobody will ever forget. The Centre also regularly invites to seminars and lectures with guest lecturers and partners from other universities.

Professor Menno P. Witter who rejected an offer of top wages and a position at the Free University of Amsterdam, is now moving to Trondheim to work at NTNU. While Edvard and May-Britt Moser research brain functions, Witter specializes in the anatomy of the brain. He knows where things happen. During the search for the spatial computer, they worked together to develop a theory on where it could be, in order to look at the right place.

”This unique way of combining disciplines places CBM in a class of its own, and is the main reason why I came here to conduct my research. The prospect of contact with several top environments at NTNU is also appealing. We cooperate with the MR Centre. While much of today’s brain research must be performed on animals, the MR technology may gradually enable us to approach the human brain,” said Witter.

Melting pot for new knowledge
Now, mathematicians are showing an interest in CBM's work. The way our brain cells are organized, involves a structure and systematism that is mathematically interesting.

CBM’s localization at the Medical Technology Research Centre where several top scientific environments are gathered creates synergy effects. Thanks to the contact with researchers at the Department of Cancer Research and Molecular Medicine next door, CBM can explore a totally new field: Virus as a tool.

Cleaned for poison and disease properties, but with the ability to penetrate cells and remain intact, viruses could become microscopic robots. The virus tool will enter the cells and switch them on and off. With such a tool, the special functions of the individual neurons within complex neural networks could be even more closely revealed.

CBM - Centre for the Biology of Memory

Facts
CBM conducts fundamental research in neuroscience to obtain knowledge about the biological processes responsible for memory.

Research Centre Managers:
Professor Edvard Moser and Professor May-Britt Moser

Board:
Professor Arnstein Finset, University of Oslo (Chairman)
Pro-Rector Julie Feilberg, NTNU
Professor Stig Slørdahl, Dean, Faculty of Medicine, NTNU
Associate Professor Jan Morten Dyrstad, Dean, Faculty of Social Science and Technology Management, NTNU

Staff:
Seven visiting professors from international universities, 9 researchers and post-docs, 5 doctoral candidates, 6 master’s degree students, 9 laboratory technicians, 1 technician.

Laboratories:
Separate laboratories at the Medical Technology Research Centre, NTNU

Contact:
Medical Technology Research Centre
NO-7489 Trondheim
NORWAY
Tel: (+ 47) 73 59 82 42
Fax: (+ 47) 73 59 82 94
Email: contact@cbm.ntnu.no
Location: Olav Kyrres gate 3, Trondheim, Norway

International partners:

Seven international professors employed in part-time positions at the Centre.

Norwegian partners:
The Centre cooperates with Professor Johan Storm at the University of Oslo and with the MR centre at NTNU.

Budget:
NOK 23.5 million/USD 3.6 million/EUR 2.8 million

Neuroscience is a new and highly interdisciplinary field. The discipline emerged in the intersection between sciences of a very different nature: psychology, neurophysiology, molecular biology, mathematics, and statistics. Neuroscience covers many levels of analysis, from molecules to brain systems and behaviour. An understanding of the brain requires technology and theories that integrate these levels of analysis.

Centre of Excellence
In 2002, the Centre for the Biology of Memory (CBM) was established as a Centre of Excellence. This establishment involves five years upgraded and intensive research activities with a potential prolongation until 2012. The annual allocation from the Research Council of Norway of NOK 10 million contributes to a long-term and intensive perspective on the research. This effort will stimulate innovative research that will yield internationally leading scientific results.