Dynamic network reconfiguration at the transition between motor programs

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The activity of a neural network is shaped by its connectome. However, this structure-function relationship is not fixed and may change dynamically, enabling rapid changes in response to new situations. In frog tadpoles, motor circuits that generate forward swimming can produce backward-thrusting struggling if the tadpole is held. Whereas swimming involves a wave of muscle contractions propagating from head to tail, struggling is a slower but powerful rhythm that propagates from tail to head. We propose that dynamic network reconfiguration occurs automatically in the spinal cord as sensory inputs change, without involving neuromodulation or feedback from the brain. Continuous sensory inputs trigger reconfiguration in tadpole motor circuit by recruiting additional groups of neurons while depressing the activity of other groups of neurons. Such recruitment/de-recruitment is achieved through changes in the biophysical properties of the neurons and their synapses. We will define these biophysical changes and determine how they reconfigure motor circuits.
The Xenopus tadpole is a unique vertebrate system to study dynamic network reconfiguration because we already know the detailed connectivity of its motor circuits, which is still the main aim of many state-of-art imaging or genetic studies in other model preparations. This will allow us to build computational models of the circuits for both swimming and struggling and analyse the dynamics at the transition between them. In turn, modelling will generate predictions about the reconfiguration mechanism, which will be tested experimentally, e.g. by using optogenetics and in situ dynamic patch clamp recordings.
The principles on how vertebrate motor circuits quickly reconfigure their connectome to generate different behaviours will not only address a fundamental neuroscience question, but also potentially provide insights for the design of robots with improved mobility and obstacle avoidance.

The aim of this project is to uncover fundamental principles about switching mechanisms between motor programs. The results will directly benefit a range of neuroscience communities listed in the Academic Beneficiaries section and contribute to improvement of UK shortage of skilled electrophysiologists. The following text outlines impacts beyond neuroscience research.

1) Neuroscience education of general public: This is the main societal impact of our project. Frog tadpoles are among the most familiar animals to the public and attract attention across different age groups. Therefore, they provide a valuable entry point to explain how the vertebrate embryo develops, and how the nervous system is organized and controls behavior. Also, tadpoles provide context for explaining how scientific research is carried out. Thus, using a simple animal is an important societal advantage of our research project. Recently our colleagues from Bristol setup the tadpole website (http://tadpoles.org.uk/) for neuroscience education of general public. This website has been attracting on average 70 visitors every day, totaling around a quarter million a year. We will update this webpage using our new results on struggling. Xenopus tadpoles go through metamorphosis to develop into frogs. A couple of years ago, our St-Andrews colleagues Prof Keith Sillar and Isobel Maynard had started to send spare tadpoles to local schools that the students can observe the metamorphosis process. This activity has received a huge enthusiasm from both students and teachers. With Isobel's recent retirement, Dr Li and Prof Sillar will continue to participate in this outreach activity.

2) Knowledge exchange with clinically applied researchers and potentially pharmaceutic companies: Development of effective clinical tools to tackle movement disorders and spinal injuries rely on understanding the basic principles underlying motor behaviours and the transition between them. This is immensely difficult in mammals. Using tadpoles presents opportunities to obtain novel, deeper insights that relate to these conditions. Both medical practitioners and pharmaceutical companies need insights from basic research to guide their own research activities and design new medicines. Direct communication with these parties can bridge gaps and help to produce better drugs.

3) Knowledge exchange with the robotic industry: Robots are taking over many tedious jobs in industrial and domestic settings. Robots that use mechanical legs for movement can go through surfaces that wheeled robots cannot enter. However, they require better stability and motion control. One difficult problem to address is what happens when a robot is stuck. Work on tadpole locomotion has shown that design details such as nonlinearities can have profound impact on robustness of motor outputs. By revealing how tadpoles quickly and robustly switch between motor programmes when the need arises, our work can potentially lead to more robust, novel robot designs.

4) Knowledge exchange with research policy makers and funding bodies: Due to their evolutionary closeness to humans, mammals have been the favorite for investigating many neuronal system functions and conditions. However, many discoveries have proven the value of choosing the simplest and most appropriate system for investigation of specific questions. Communicating the findings from this project to funding decision-makers will help to support the use of model animals and reduce experiments with adult mammals. Indeed, using tadpoles as a model animal to study motor control is internationally recognized but is carried out almost entirely in the UK. With Prof Roberts's and Dr Soffe's retirement, the tadpole research has been shifting to Scotland (Prof Keith Sillar, Drs Wen-Chang Li and Hong-Yan Zhang). The success of research outputs from this model system will continue to raise the profile of UK research.