Computational approaches to neuroscience research

Modern neuroscience research aims to increase our understanding of the biological processes going on inside brains and nerve cells. By doing so, we learn how brains control all aspects of behaviour, and we may one day be able to explain the physical basis for the most complex aspects of humanity such as consciousness. Understanding brain function is also crucial to the development of treatments for neurological disorders or damage. To tackle such difficult problems, neuroscience research draws on a huge range of experimental approaches, ranging from measurements of behaviour, through recordings of the electrical activity of individual nerve cells, to the modelling of sub microscopic processes that govern how molecules in nerve cell membranes change their shape in response to chemical or electrical signals. Increasingly, several of these techniques must be used in parallel to understand the functioning of 'the system' as a whole. Work in my laboratory addresses questions relating to the control of aimed limb movements. For example, how do sensory nerve cells signal a touch on the body surface? How do they then pass this information to other nerve cells that transform it into a pattern of activity that controls sets of limb muscles to produce a scratching movement aimed at the location of the touch? We film such movements and measure the movements very precisely, while recording and manipulating the electrical signalling of individual nerve cells to investigate their roles in the control system. This work is carried out in an insect, the locust, but the principles of organisation that we uncover can be related to brain function of other animals, including humans. In our most recent work we are setting out to develop new techniques to record and analyse the activity of not only single nerve cells, but groups of cells acting together. These multielectrode array recording techniques yield very complex signals that require considerable computational expertise to analyse. Part of our work, carried out with leading experts in signal processing, is to develop such analysis techniques, which will also be used for the analysis of recordings made from the brains of human patients during surgery. My expertise is in making recordings from nerve cells, but to take our collaborative work forward I now need to learn a new suite of techniques to process the new types of data that we will be gathering. The main purpose of this Fellowship is provide me with such training. I will attend courses and undertake hands-on training in the relevant techniques, some in the labs of my collaborators in Leicester and Germany. I will learn the use of specific software, but also the underlying principles of analysis. During the course of the Fellowship I will apply these new techniques to our data and attempt to answer some challenging questions about the control of aimed limb movements. I will also have the time to publish the results of a great deal of our work carried out over the last few years. This intensive re-training and research requires that a concentrated and extended period of time is devoted to it. The Fellowship will provide this opportunity, and will be matched by a commitment from my University to free me of remaining duties for the same period. In the end I will be in a much stronger position to continue to develop our research in new directions, and to train young researchers and students who will go on to strengthen the UK's position as a leading country for both basic and biomedical neuroscience research.

Recent research in my lab has focused primarily on the neuronal control of aimed limb movements, and on analyses of visual processing during phase transition in locusts. We have generally relied on single-cell intracellular recordings and extracellular electromyogram recordings, often coupled to movement kinematic analyses, to address our key research questions. My expertise lies in these specific areas. I now wish to apply new techniques to take this research in new directions, and to achieve this have obtained funds to support an interdisciplinary collaboration that will centre on multi-electrode array recordings. These recordings generate complex data that require specialist expertise to analyse, which is the forte of my collaborators. Nevertheless, to capitalise on this opportunity, I need to re-train myself in the use of appropriate software (Matlab and Python), and the fundamentals of relevant computational approaches (signal processing, image processing and biomechanical modelling). This 18 month Fellowship will allow me to achieve 4 main goals. First, it will provide me with the opportunity to obtain appropriate training in programming and data analysis techniques to update my existing knowledge. Second, it will enable me to carry out analyses of our extensive existing and new datasets to address questions that would not otherwise be tackled. Third, it will enable me to use my expertise in electrophysiological recordings to develop our new multielectrode array recording techniques. Fourth, I will be able to finish the analyses for, write up and submit, a number of related research papers. The long-lasting and very valuable outcome of the Fellowship will be to strengthen my ability to develop further multidisciplinary collaborations, to contribute more effectively to innovations in our joint work, and to train postdoctoral researchers and students in a wider range of key techniques in modern neuroscience.

The main aim of this Fellowship application is to provide me with the opportunity to re-train with new skills in computational neuroscience that will influence all of my future scientific work. The impacts will therefore be widely distributed across all the different research projects that I participate in and supervise. Secondary aims are to complete specific experiments and publish research papers that demonstrate how the nervous system controls movements. The most immediate tangible benefits to society will come from my collaborative work with neuroengineer Prof Rodrigo Quian Quiroga. Our ongoing work, supported by the training and analyses that I will undertake during the Fellowship, will contribute to a detailed knowledge of how nerve cells represent information about directed limb movements. Such questions are very important to neuroscientists seeking to understand human brain function, and are also intrinsically related to clinical applications such as the development of prosthetic devices driven by brain signals. The signal processing technology that we develop will be used in clinical research to improve the detection and classification of neuronal signals recorded from the brains of awake patients. Beneficiaries of our work will therefore include not only the scientists carrying out the work and our academic collaborators around the world, but members of the public, clinicians and roboticists. Members of the public will benefit in the longer term from improvements in medical interventions that improve their quality of life, such as the development of neuroprosthetic devices and autonomous limbed robots. Transfer of benefit to clinicians and patients will take many years, but have long-lasting consequences. Our use of an insect to develop our understanding of movement control contributes to the reduction of experiments on vertebrates, which is a key BBSRC goal. As a result of the training that I will undertake, I will be in a better position to train and mentor students, postdoctoral researchers and technicians in specialised research techniques, and in transferable skills that improve their ability to perform their jobs and enhance their career prospects. These benefits will be long lasting. My work will therefore help to provide the skilled researchers and technicians needed for both academic research and industrial research and development in the UK, which is a BBSRC Strategic Goal. Because I collaborate internationally and host visiting students and scientists, such benefits will also extend beyond the UK. A second strand of my ongoing research is to develop an understanding of the neuronal mechanisms underlying the formation of devastating locust swarms. This work, carried out in collaboration with colleagues at the University of Cambridge, may lead to an improved ability to predict swarm outbreaks, and to better control strategies. Such improvements would have significant impacts on the quality of life and economic strength in affected countries. All of our work is published in prestigious scientific journals and presented at international conferences. In addition, during the course of my Fellowship I will co-organise with Quiroga a 1-day public workshop on signal processing, including its impact on medical research and interventions. Our work is summarised in public open days and media communications as appropriate to its progress. Information is always available from our dedicated public web pages. The main concepts underlying our work are attractive and easily comprehensible to a general audience. Dissemination and public engagement will be facilitated by the University Press Office. In the past my work on mechanisms of righting behaviour in insects attracted international TV coverage, and the work of my collaborators is regularly featured in the international media.