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EASTBIO Involvement of sodium pumps in the postnatal maturation of spinal circuits for walking


School of Psychology

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Prof G Miles , Dr S Sharples No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

For parents, the moment of their child’s first steps is a remarkable and memorable one. For this to happen, the child must first stand upright and support their own weight. The ability to take these first steps is due to maturation of neuronal circuits within the spinal cord, which coordinate the activity of postural muscles with that of more than 80 muscles of the legs to produce walking movements.

We have recently shown that the ubiquitous Na+-K+ exchange pump plays an important role in adapting motor control networks of the spinal cord in an activity-dependent and homeostatic manner (Picton et al., 2018; Sharples et al., 2020). This dynamic regulation of spinal neurons is thought to involve sodium pumps containing an Alpha3 subunit. We have exciting preliminary data suggesting that expression of the alpha3 subunit increases during a critical developmental window when complex, weight-bearing locomotion emerges and may therefore be a key contributor to the necessary maturation of spinal motor networks.

To address this hypothesis, the student will deploy a complement of state-of-the-art tools to probe the contribution of sodium pumps to the maturation of spinal circuits in the postnatal mouse, where fully mature locomotor behaviours emerge during the first three postnatal weeks. Experiments will be conducted in wildtype, as well as genetically modified mice harbouring a loss of function mutation in the alpha3 subunit of the sodium pump. The use of this genetically modified model will enable us to study the causative links between alpha3-containing sodium pumps and the development of complex movements. We will utilise electrophysiological, imaging, biochemical, and molecular genetic techniques to investigate cellular, synaptic and network mechanisms underlying sodium pump mediated control of spinal motor networks during development.

This project will advance our understanding of the role that a novel homeostatic regulator, sodium pumps, plays in the development and ongoing control of neural circuits that are critical for movement. Increasing our understanding of adaptive plasticity in spinal networks during postnatal development, as complex, adaptable movements emerge, will help identify novel therapeutic targets for the attenuation of maladaptive plasticity and homeostatic dysfunction in disease.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership http://www.eastscotbiodtp.ac.uk/how-apply-0. This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition. For international candidates, the University of St Andrews will cover the Home-International fee difference. Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

As part of your online application please upload the EASTBIO Application Form, academic transcripts, and ensure two references (using the EASTBIO reference form) are provided by the deadline.

References

1. Picton, L., Nascimento, F., Broadhead., Sillar, K., Miles, GB., (2017). Sodium pumps mediate activity-dependent changes in mammalian motor networks. Journal of Neuroscience. 37(4): 906-921.
2. Sharples, S.A., Vargas, A., Lognon, A.P., Young, L., Shonak, A., Cymbalyuk, G., and Whelan, P.J. (2020). Dynamics of episodic and continuous rhythmic activities from a developing central pattern generator. bioRxiv. DOI: https://doi.org/10.1101/2020.09.08.288266.
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