Viruses and young cuckoos lead the way in the brain

(14.10.08) Harmless viruses and genetic "young cuckoos" are going to reveal the answers as to how the brain establishes where we are. The understanding of our sense of locality will be the first higher brain function that we understand at a molecular level.

Previously, researchers at the Kavli Institute at NTNU discovered the brain’s own GPS – a particular type of cells from which the sense of locality stems. Now, they are adopting gene technology in order to dig deeper: They want to know how advanced mental phenomena such as memory, sense of locality and decisions come into existence in the interaction between millions of nervous cells.

This is the first time researchers will succeed in describing and explaining down to the least detail how a so-called higher brain function works mechanistically. And everything takes place in rat brains.

The Institute has been awarded a grant of NOK 20 million from the European Research Council (ERC), via the programme ERC Advanced Investigator Grants.

Shining researcher stars
”This is primarily a recognition of the fantastic work performed at the Kavli Institute,” says NTNU Rector Torbjørn Digernes. ”Mr. and Mrs Moser have long been shining stars on the researcher sky. They are an inspiration for everyone else.”

”The 20 millions are very welcome,” Professor Moser says. ”This project brings Norwegian brain research another step forward. It is also a huge inspiration for basic research on the mechanistic basis for mental functions. It will bring us much closer to an understanding of how nervous cells produce mental functions, and in the long run contribute to the treatment of diseases attacking the brain.”

Viruses as messengers
It is a well-known fact that the experience-based functions in question are the result of interaction between thousands of nervous cells scattered in the brain, and millions of contact points between them. However, it has been impossible to study this through experiments. Methods for stimulating selected cell types in the same brain area have been lacking.

New gene technology changes this situation. The project uses viruses to switch certain nervous cells on and off. We are talking harmless viruses here that are unable to copy themselves and cause damage. The only function of the virus is to be the messenger: It brings an alien gene in among the brain cells, finds the right cell type and delivers the gene there. The cells absorb the gene and make it their own. Then they start producing the protein that the gene has the ”recipe” of. This changes the cell’s characteristics.

Genetic "young cuckoos"
”The new genes placed inside the nervous cells are a bit like young cuckoos, ” says Professor Edvard Moser at the Kavli Institute. ”They are a bit different, but regarded as part of the family. We know the "young cuckoo's" characteristics and how to make it sing and keep quiet. Or, as we call it: switch the genes on and off. That is the stroke of genius and what enables us to study which cells that do what inside our brains," Moser explains.

The new genes can be switched on and off by for instance adding certain chemicals to the rats’ drinking water. When the genes are switched on (no chemicals added), they produce proteins. When the genes are switched off (chemicals added), the protein production stops. The proteins are important for the cells to be able to send certain types of signals. By controlling how the signals are sent, we can control the activity in the cells we are studying. This way, we can study the cell’s function.

Searching for totality
The project uses the discovery of the brain’s sense of location as the starting point. The research group in Trondheim has mapped many different types of cells that work together in networks. So far, they have only established how the different types work, but not the function of the totality. But now they will.

They start off by gaining exact knowledge about how the brain estimates where we are. With the new gene technology, this is possible. The sense of locality is the first of the so-called higher cognitive abilities that we may be able to understand at a very basic level.

The project is highly interdisciplinary. The core elements are neurophysiology and neuropsychology measuring signals from many nervous cells at the same time as rats find their way through labyrinths.

European funding for basic research
The European Research Council (ERC) has two programmes for funding of top research. The first, introduced in 2007, is the ERC Starting Grants, that Norway received twice, both for the Kavli Institute. These grants provide substantial funding for new researchers so they can build up their own group.

The second programme is the ERC Advanced Investigators Grants, awarded to internationally leading researchers. Here, we are talking research that pushes research frontiers forward and contributes to scientific breakthroughs. The projects are typically innovative, path-breaking and high-risk, but with major scientific potential. The ERC Advanced Investigators Grant was awarded for the first time in 2008. The results for physics and the Humanities were presented earlier this year, but no Norwegian projects were awarded grants. The final group is the Life Sciences, where the Kavli Institute once again has been invited to contract negotiations. A total of 78 winners of the Advanced Grants are European, of which two are Norwegian. European neuroscience projects were awarded a total of 10 grants.

Contact person:
Edvard Moser, Director of the Kavli Institute for Systems Neuroscience. NTNU
Telephone: (+ 47) 930 54 884 / (+ 47) 73 59 82 78
Email: edvard.moser@ntnu.no

Press release from ERC (pdf)