Final Report Summary - C. ELEGANS MOTION (Neural control of locomotion in c. elegans worms: Combination of mathematical modeling and molecular-cellular biology)
The general aim of the project was to understand how nervous system controls undulatory locomotion. Specifically, we wanted to find out the key neural mechanisms responsible to behavioural transitions in a tiny nematode worm c. elegans. This was achieved using a combination of computational, theoretical and experimental approaches, in collaboration with the lab of Prof. Paul Sternberg from California Institute of Technology, United States of America (USA).
The main results can be characterised as:
1. The decision made by a nematode worm to move in a particular direction is made on the level of interneuron network. This is done by breaking symmetry between activities of downstream network of motor neurons (there are two groups of motor neurons: one controlling forward and second backward motion). More precisely, the worm moves in the direction controlled by motor neurons whose activities are larger.
2. The decision making locomotory interneuron circuit has an inhibitory character, i.e. most of its interneurons have inhibitory synapses.
3. Only collective activity of the whole interneuron circuit is important for locomotory output. This means that activity of any single interneuron does not have a critical effect on the circuit function.
4. The experimental results can be best explained if we assume that each interneuron can have a mixed synaptic polarity. That is, some of the synapses coming out of an interneuron can be excitatory and some can be inhibitory. This unexpected result came out as a result of interaction with experimentalists who do neurophysiology of c. elegans. They noted that a single synapse generally has multiple receptors, some characteristic for excitatory and some for inhibitory connections. This rather does not happen in the vertebrate brain, where synapses usually have a single polarity.
Conclusions and potential impact:
We hope that the kind of modelling of the biological system we performed can be used and extended by others. We provided not only qualitative but also quantitative explanation of the experimental data on c. elegans locomotion, using mathematical modelling. More generally, up to recent years mathematical models in biology were not treated seriously by traditional biologists. This has been changing recently due to new fields such as computational neuroscience or computational biology (Informatics). We hope that due to projects like this one more traditional biologists will appreciate mathematical modelling as an important part and tool in biology.
Scientific and socioeconomic implications:
The project on neural control of c. elegans locomotion is not an isolated project, but rather a part of a larger scientific enterprise, which is called computational neuroscience or neuroinformatics. These two related interdisciplinary fields are relatively new, but nevertheless are rapidly expanding in the most advanced countries. Their main goals are similar, i.e. they try to understand the functioning of the brain (or generally nervous system) by mathematical modelling and data collection. This interdisciplinary approach can potentially produce important results for society because understanding neuronal processes can have many benefits; for example, in medicine in treating various neurological disorders (autism, schizophrenia, Alzheimer), or in technology in constructing 'intelligent devices' that would perform complex and difficult work unachievable for human.
The field of computational neuroscience is practically new in Poland and therefore it needs promotion. The researcher Jan Karbowski has been doing work in this direction. In particular, he has been teaching advanced neuroscience courses at nearby Warsaw University for MSc and PhD students. The two main courses are 'Introduction to neurodynamics and neuroinformatics' and 'Mathematical models of learning and memory in the brain', which are quite popular among the students. This popularisation effort also resulted in one student obtaining his MSc under the guidance of Dr Karbowski within the project. Dr Karbowski gave several seminars promoting the project on c. elegans and generally computational neuroscience. Additionally, he wrote a popular review article promoting the field in the physics and mathematics community in Poland entitled 'What can a mathematician do in neuroscience?'. It is important to note that during the course of the project Dr Karbowski was promoted to an Associate Professor position both in the Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences (where the project has been conducted) and in the Warsaw University where he teaches. Thus, the Marie Curie grant has had a positive impact on Dr Karbowski scientific career. Apart from that Dr Karbowski received a grant from the Polish Ministry of Science and Education to perform research on modelling brain energy metabolism within a general field of computational neuroscience. Thanks to this grant and the grant from Marie Curie Actions, it was possible to perform research and publish two papers on brain metabolism.
The main results can be characterised as:
1. The decision made by a nematode worm to move in a particular direction is made on the level of interneuron network. This is done by breaking symmetry between activities of downstream network of motor neurons (there are two groups of motor neurons: one controlling forward and second backward motion). More precisely, the worm moves in the direction controlled by motor neurons whose activities are larger.
2. The decision making locomotory interneuron circuit has an inhibitory character, i.e. most of its interneurons have inhibitory synapses.
3. Only collective activity of the whole interneuron circuit is important for locomotory output. This means that activity of any single interneuron does not have a critical effect on the circuit function.
4. The experimental results can be best explained if we assume that each interneuron can have a mixed synaptic polarity. That is, some of the synapses coming out of an interneuron can be excitatory and some can be inhibitory. This unexpected result came out as a result of interaction with experimentalists who do neurophysiology of c. elegans. They noted that a single synapse generally has multiple receptors, some characteristic for excitatory and some for inhibitory connections. This rather does not happen in the vertebrate brain, where synapses usually have a single polarity.
Conclusions and potential impact:
We hope that the kind of modelling of the biological system we performed can be used and extended by others. We provided not only qualitative but also quantitative explanation of the experimental data on c. elegans locomotion, using mathematical modelling. More generally, up to recent years mathematical models in biology were not treated seriously by traditional biologists. This has been changing recently due to new fields such as computational neuroscience or computational biology (Informatics). We hope that due to projects like this one more traditional biologists will appreciate mathematical modelling as an important part and tool in biology.
Scientific and socioeconomic implications:
The project on neural control of c. elegans locomotion is not an isolated project, but rather a part of a larger scientific enterprise, which is called computational neuroscience or neuroinformatics. These two related interdisciplinary fields are relatively new, but nevertheless are rapidly expanding in the most advanced countries. Their main goals are similar, i.e. they try to understand the functioning of the brain (or generally nervous system) by mathematical modelling and data collection. This interdisciplinary approach can potentially produce important results for society because understanding neuronal processes can have many benefits; for example, in medicine in treating various neurological disorders (autism, schizophrenia, Alzheimer), or in technology in constructing 'intelligent devices' that would perform complex and difficult work unachievable for human.
The field of computational neuroscience is practically new in Poland and therefore it needs promotion. The researcher Jan Karbowski has been doing work in this direction. In particular, he has been teaching advanced neuroscience courses at nearby Warsaw University for MSc and PhD students. The two main courses are 'Introduction to neurodynamics and neuroinformatics' and 'Mathematical models of learning and memory in the brain', which are quite popular among the students. This popularisation effort also resulted in one student obtaining his MSc under the guidance of Dr Karbowski within the project. Dr Karbowski gave several seminars promoting the project on c. elegans and generally computational neuroscience. Additionally, he wrote a popular review article promoting the field in the physics and mathematics community in Poland entitled 'What can a mathematician do in neuroscience?'. It is important to note that during the course of the project Dr Karbowski was promoted to an Associate Professor position both in the Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences (where the project has been conducted) and in the Warsaw University where he teaches. Thus, the Marie Curie grant has had a positive impact on Dr Karbowski scientific career. Apart from that Dr Karbowski received a grant from the Polish Ministry of Science and Education to perform research on modelling brain energy metabolism within a general field of computational neuroscience. Thanks to this grant and the grant from Marie Curie Actions, it was possible to perform research and publish two papers on brain metabolism.
