In love with the spinal cord
How does the nervous system adjust the sensitivity in our movements? That is one of the great mysteries which Rune Berg hopes to learn more about through the development of advanced mathematical models.
By Eline Mørch Jensen
Rune Berg is a physicist with a PhD in biophysics and a special interest in neuroscience. For the last five years he has worked with professor of statistics, Susanne Ditlevsen, on how to deal with stochastic signals in the nervous system. The research project "Dynamic systems" is a further development of this collaboration.
- What I do is measure the flow in each cell, not in living human beings, but in rats and turtles. If you compare tissue from a rat brain and a human brain it is hard to see much of a difference, says Rune Berg, adding:
- I work mostly with the spinal cord of turtles from our animal stables. I have almost fallen in love with the spinal cord - because the problem of how networks of nerve cells communicate and produce functions are the same here as it is in the brain, but the spinal cord is much less complicated and its function is well defined. Therefore, I imagine that an understanding of the spinal cord function will be an important key to understanding the brain.
So turtles do actually have a spine under their shell - how do you get to it?
- It requires a surgical procedure which involves a saw, but yes, they actually do. The reason for using these turtles is that they are vertebrates with legs just like us, and even though they from a forensic point of view are dead the cells can stay alive for a very long time.
How does measuring the electric flow in the nerve cells of rats and turtles make us wiser?
- We're at the faculty of health and medical sciences which rather clearly indicates what we are here for: preventing diseases and healing lives, which at times actually annoys me a little because in my view what I do is basic research first and foremost.
- The goal is an understanding of how communication between thousands of neurons can organize itself in the form of electrical activity appropriate for the organism. The body’s movements are controlled by muscles which in turn are controlled by nerve activity, but where does the activity come from and how does it arise? This is first and foremost a fundamental scientific problem the purpose of which is to broaden our overall understanding of ourselves and of nature, but of course we use the basic scientific knowledge to prevent illness and to cure, says Rune Berg, adding:
- One of the reasons to work with these measurements is to understand how the nervous system - not to mention networks within the system - works. As in how they are interconnected and what their shared architecture looks like. Because in order to understand a dynamic system, that is an active system that produces something, you have to look at the dynamics of units as well as examine how they are connected and interact.
Don´t you run the risk of inventing networks – that is, seeing contexts which do not actually exist?
- Yes, there are many pitfalls associated with this work, so that risk is definitely there. Much of our work is about proving that the correlations are not simply epiphenomenal. This is exactly why we need to develop better and more precise measurements. Mapping networks can be a completely insurmountable task which is why some scientists actually consciously try to construct artificial networks in order to study and learn from their dynamics and compare them to the networks we are familiar with, says Rune Berg, adding:
- It may sound weird, but the very act of creating networks on the computer may in some cases lead to the conclusion that there is good evidence for one or the other and so may help us a step further on the road to analysing the readings.
- But it is difficult to do both the experimenting and the data processing so it is really important and positive that the method researchers, i.e. the mathematicians and statisticians, take care of this field as it is their speciality.
There are currently five people from the Department of Neuroscience and Pharmacology involved in the research project "Dynamic systems" including two doctors, two physicists, a molecular biologist and an additional five persons, equivalent to five FTEs, to be appointed as postdocs and PhD´s and attached interdisciplinarily across the different fields.
- The project is to a large extent a development of our ongoing work where we collect parallel or closely related data through extra- and intra-cellular measurements, and we are now also in the process of measuring using multi-electrodes.
- Neuroscience is such a large field that at our annual meetings in the U.S. have around 35,000 participants. We each have our specialties, but many of us are electro-physiologists and are particularly interested in fully developed networks. In our group we have chosen to look at how it works when it works, or in other words, when a network is fully developed and not in the process of being developed such as in a foetus for instance.
- Some of my colleagues make voltage-dependent colour measurements, a technique where you for instance inject green dye and then allow the nerve network to conduct its normal function and use the colour to detect the activity. This is done specifically by surgically exposing the brain of an animal, a ferret for instance, anaesthetized of course, in order to add the dye. When the nerve cells are active, they change colour, which you can use to study their functions. Some cells are big, they can be up to one millimetre, and can even be seen with the naked eye.
- One of my colleagues, Jørn Dybkjær Hounsgaard, who is a medical doctor, is looking at calcium in nerve cells. Calcium is present in very low concentration in the cells at rest. With calcium-dependent dyes in the cells the penetration of calcium during nerve activity can be detected microscopically and it is this activity which he measures, Rune Berg explains.
He stresses that Jørn Dybkjær Hounsgaard does not use these measurements as a regular doctor would do, but to find some kind of order in these networks, among other things in an attempt to understand the disease ALS. It seems to be the case for ALS patients that the cells most sensitive to calcium are the ones to die first.
- The specific function - or rather the mystery – in the nervous system for which I have a particular concern and which we examine in the context of this project, is how populations of neurons optimize the precision of the motor control. When a muscle provides a certain amount of force it is important that it does so with a corresponding precision. The precision of the power is actually just as important as the power itself, says Rune Berg, adding:
- This can be illustrated with an example from our world: the fingers we use to keep or carry our body weight when we climb up a wall are the same that we use to make very fine movements, as in cardiac surgery for instance. But the force that our finger muscles apply during cardiac surgery naturally needs to be applied with a precision that corresponds to this task and not with the force required to lift your own weight on a climbing wall, for example.
And Rune Berg states:
- The very question of how the nervous system constantly provides active adjustments of the sensitivity of our movements is one of the great mysteries, and it can be generalized to all brain functions, not just muscle control. And it is one of the things we are hoping to learn more about through the development and use of models in this research.
About Rune W. Berg
Rune Berg got his PhD in biophysics from University of California San Diego in 2003. After a post doctoral training in Taiwan and in Denmark he joined the department of neuroscience and pharmacology at the University of Copenhagen as an associate professor in 2008.