Jeanette Hellgren Kotaleski - a broad research interest in the complex nervous system

The nervous system is very complex, not least in us humans. But if we can understand the basics of it, we also have a good starting point for receiving further insights into how people work, Jeanette Hellgren Kotaleski explains. An understanding of the brain, will of course transform the treatments of brain diseases.

Computational biology is about describing biological systems with the help of equations. Jeanette Hellgren Kotaleski and her colleagues work at the Department of Computational Biology at the School for Computer Science and Communication. Her area of specialization is computational neuroscience and she uses advanced equations to simulate the dynamics of the nervous system.

The nervous system affects us in a range of different ways. With the help of the nervous system we can react to external stimuli and thereby sense things and decide to act on those sensations in a goal-directed way. Here learning is important. Different motor skills, such as lifting a hand or waving ones toes, start in the brain, and here the basal ganglia are an important forebrain structure involved.

Jeanette Hellgren Kotaleski focuses on motor systems. She mainly wants to understand the neural mechanisms underlying information processing, rhythm generation and learning in such systems. Hellgren Kotaleski collaborates with researchers at the Karolinska Institutet, experimentalists, who conduct experiments, and experimental measurements that are important for constraining the computational models. Ideally, models should also inspire and direct experimentalists to pursue specific new experiments.

In this context, close collaboration between researchers producing models, like for example Jeanette Hellgren Kotaleski, and experimentalists generating data, assures  that both modellers and experimentalists  can get faster feedback on their work. The alternative would have been for researchers like Hellgren Kotaleski to work alone only build models based on already published data and then in turn publish their models, hoping that some experimentalists at a later stage plan their experiments inspired from the model predictions.

“A large part of the research work also deals with keeping oneself updated on the newest research developments in the field”, says Hellgren Kotaleski. “Here one needs to follow both the development in the modeling community, but also stay updated on new experimental work.”

Jeanette Hellgren Kotaleski and collaborators at KI have done combined experimental-modeling research on the lamprey, one of the oldest vertebrates, that has existed for 560 million years. Humans and lampreys are, however, similar in many ways regarding for example the basal ganglia. The basal ganglia are involved in, among other things, decision making in humans and other vertebrates. And decisions can be of a relatively simple nature, such as taking a step either to the right or left, but also quite advanced decision making goes on when selecting between alternative strategies to achieve a future goal. Here uncertainties, such as previous experiences, are important for how the basal ganglia contribute. As there are many similarities between the basal ganglia between lampreys and human beings, it is indeed possible to apply certain results from the studies on lampreys on humans.

However, human existence is somewhat more complex than that of lampreys. Unlike lampreys, humans live in a world where we do not only receive impressions from the world around us, eat and reproduce but also, on a daily basis, have to make a number of more or less difficult decisions on everything from paying bills, to where to live and whom do socialize with.

Using as simple animal models as possible is one important strategy to understand aspects of the brain. But also it is necessary to help researchers integrate data and knowledge from different species, different scales, e.g. subcellular, cellular, network, organ, and from using different approaches (imaging, electrophysiology, gene knockout, insights from diseased brains, etc). To facilitate such a process worldwide, the International Neuroinformatics Coordinating Facility (INCF) was established in 2005. Their role is to coordinate and stimulate an infrastructure, which promotes for instance sharing of data, models, and computing resources to the international research community to speed up this process.  Researchers will eventually need to study and understand the brain in its entirety. It is indeed an entirety that is comprehensive and complex. On one of the most basic levels, it is a matter of one signal being sent from one nerve cell to another. But there are 100.000.000.000 nerve cells in the brain, and most nerve cells have 1000 of connections with other cells.  

“This complexity also explains why it is difficult to figure out how to treat brain diseases. Diseases of the brain are usually diagnosed in terms of symptoms and syndromes, an approach that makes it very difficult to produce definitive diagnoses, or to select the patients who will benefit from a particular therapy. Similarly, most treatments are designed to manage symptoms, because the underlying disease mechanisms are not understood well enough. This also explains why companies such as AstraZeneca close down their research on brain diseases. It is too expensive to develop new drugs for brain diseases since drug development becomes based on much ‘trial and error' when the basic mechanisms are not known”, says Jeanette Hellgren Kotaleski.

It is indeed important to understand the brain to cure its diseases. Through understanding the brain it is also possible to develop information processing systems that can adapt to a non-predictable environment and learn based on experience. Understanding the brain will for sure, sooner or later, thus open the road for the development of both compact and energy efficient systems with the long-term potential to achieve brain-like intelligence. Already, research (The Human Brain Project) is ongoing with the aim of simulating the brain in supercomputers.

Jeanette Hellgren Kotaleski’s interest in the nervous system is broad.

“I think the brain is one of the most fascinatings thing we can do research on. I have always been interested in understanding it for the sake of understanding”, says Jeanette Hellgren Kotaleski and adds “I could conduct research on anything to do with the brain. Searching for the mechanisms underlying the functioning of the brain will for sure have tremendous consequences for the humanity in the long run.”

Emma Bayne

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