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EASTBIO Crafting Precision in Movement: Neuromodulatory Control of Motoneuron Recruitment


   School of Psychology

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  Prof Gareth Miles, Dr Maarten Zwart  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

A critical feature of the central nervous system (CNS) is the ability to adapt neural activity so that behaviours can be adjusted to suit the varying demands of different environments and organismal states. The importance of this adaptability is particularly evident when one considers the range of movements that must be performed daily and the array of neurological diseases that involve impairments in movement.

This PhD research project aims to advance our understanding of the mechanisms by which neural circuits within the spinal cord create a range of adaptable movements. We plan to address this by focussing on the output neurons of these circuits, motoneurons, which control muscles and therefore all movements. Different classes of motoneurons are recruited depending on the type of movement required; for example, fast and strong movements versus ‘steady’ and less powerful movements. The mechanisms governing the orderly recruitment of different classes of motoneurons has historically been thought to relate to static properties such as motoneuron size. However, we have recently found that other features, such as the complement and properties of ion channels expressed by each motoneuron subtype (Sharples and Miles, eLife, 2021), represent important determinants of motoneuron recruitment. We also know that the properties of these ion channels can be adjusted by a host of chemical signals called neuromodulators (Eleftheriadis et al, PNAS, 2023). Taking these findings together, we hypothesise that the ability to readily adjust and fine tune movement involves neuromodulation of ion channels, and the subsequent refinement of motoneuron recruitment order.

This project will interrogate the mechanisms by which neuromodulators dynamically adjust motor output, from single cell to network levels, by using a combination of advanced techniques to probe neural function within in vitro rodent models. The project will provide opportunities to gain expertise in a range of cutting-edge neuroscience techniques including whole cell patch-clamp electrophysiology and live multiphoton imaging. These techniques will be utilized in combination with pharmacological and molecular genetic tools that enable us to manipulate neuromodulatory systems. Overall, this approach will enable us to determine the roles of neuromodulators in adjusting motoneuron properties, refining motoneuron recruitment order and ultimately producing adaptable motor network output. 

HOW TO APPLY

Application instructions can be found on the EASTBIO website- http://www.eastscotbiodtp.ac.uk/how-apply-0

1)     Download and complete the Equality, Diversity and Inclusion survey.

2)     Download and complete the EASTBIO Application Form.

3)     Submit an application to St Andrews University through the Online Application Portal

Your online application must include the following documents:

-         Completed EASTBIO application form

-         2 References (to be completed on the EASTBIO Reference Form, also found on the EASTBIO website)

-         Academic Qualifications

-         English Language Qualification (if applicable)

Unfortunately due to workload constraints, we cannot consider incomplete applications. Please make sure your application is complete by 27th November 2023

 CONTACT

Queries on the project can be directed to the project supervisor.

Queries on the application process can be directed to Rachel Horn at [Email Address Removed]

UKRI eligibility guidance: Terms and Conditions: View Website International/EU: View Website

Biological Sciences (4) Medicine (26)

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend at UKRI standard rate and UK level tuition fees. The University of St Andrews will cover the Home-International fee difference.

References

Sharples, S.A. and Miles, G.B. (2021). Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development. eLife. 10: e71385. DOI: 10.7554/eLife.71385.
Eleftheriadis PE, Pothakos K, Sharples SA, Apostolou PE, Mina M, Tetringa E, Tsape E, Miles GB, Zagoraiou L (2023). Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses. Proceedings of the National Academy of Sciences (PNAS), in press.
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