Development of spinal circuits

For many parents, the moment of their child’s first steps is a memorable one. For this to happen, one must first stand upright and support their own weight. The spinal cord is a key part of the nervous system that controls automatic movements such as walking require the precise activation of more than 80 muscles of the legs. The ability to take these first steps is due to maturation in how neuronal circuits in the spinal cord function and communicate with the brain.

One focus of my postdoctoral work, being conducted in the Laboratory of Professor Gareth Miles at the University of St Andrews, is to understand plasticity in spinal circuits during early postnatal life.

To address this, I am studying changes in spinal cord function during postnatal development in the mouse. The newborn rodent progresses from a state of immobility during the first postnatal week, gaining the ability to support its own body weight and perform rudimentary movements by week 2. By the third week, motor behaviours are more consistent with that of the fully mature animal.

This model system therefore provides a unique opportunity to study adaptive changes in neural circuits that control defined and measurable behaviours.

3 main focuses of this work:

Maturation of intrinsic properties and their contribution to motoneuron recruitment.
Activity-dependent regulation of motoneuron excitability by sodium potassium ATPase pumps.
Relative weighting of synaptic and intrinsic properties for motoneuron recruitment.

Tools

In vitro Preparations

Electrophysiology

Outputs

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: https://doi.org/1 0.7554/eLife.71385.

Jean-Xavier, C.*, Sharples, S.A.*, Mayr, K.A., Lognon, A.P., and Whelan, P.J. (2018). Retracing your footsteps: developmental insights into spinal network plasticity following injury. Journal of Neurophysiology. 119 (2): 521-536. DOI: 10.1152/jn.00575.2017.

Dalrymple, A.N., Sharples, S.A., Osachoff, N., Lognon, A.P., and Whelan, P.J. (2019). A supervised machine learning approach to characterize spinal network function. Journal of Neurophysiology. 121 (6): 2001-2012. DOI: 10.1152/jn.00763.2018

Selected Conferences

Sharples, S.A., and Miles, G.B. Fast motoneurons are not just ‘big’ slow motoneurons: roles for active properties in maintaining the orderly recruitment of motoneuron subtypes. Motor Systems Symposium. Salk Institute, La Jolla, CA, USA. November 2022. (Talk)

Sharples, S.A., and Miles, G.B. M-type potassium currents shape the recruitment of motoneuron subtypes. Society for Neuroscience. San Diego, CA, USA. November 2022. (Poster)

Sharples, S.A. and Miles, G.B. Postnatal integration of active properties shapes motoneuron recruitment. International Motoneuron Society Meeting. Banff, AB, Canada, June 2022. (Talk)

Sharples, S.A. Moving beyond the size principle: How the integration of active properties shapes motoneuron recruitment during postnatal development. The Online Motor Unit Seminar Series. February 2022. (Talk)

Sharples, S.A. and Miles, G.B. (2021). Persistent and hyperpolarization-activated inward currents shape fast and slow motoneuron recruitment during postnatal development. Poster presentation at the Society for Neuroscience, Chicago, IL, USA, November, 2021. (Poster)

Sorrell, F.L., Hooper, F.W., Sharples, S.A., Akkuratov, E.E., Aperia, A., Miles, G.B. (2021). Effects of the rapid-onset-parkinsonism gene mutation T613M on spinal motor networks in mice. Poster presentation at the ATP1a3 in Diseases Symposium, Stockholm, Sweden, September 2021. (Talk)

Sharples, S.A., Sorrell, F.L., and Miles, G.B. (2019). Intrinsic property maturation drives the orderly recruitment of slow and fast lumbar motoneurons during postnatal development. Poster presentation at the Society for Neuroscience, Chicago, IL, USA, October 2019. (Poster)

Sorrell, F.L.*, Sharples, S.A., Sillar, K.T., and Miles, G.B. (2019). Post discharge activity of spinal motoneurons across postnatal development in mice. Poster presentation at the Society for Neuroscience, Chicago, IL, USA, October 2019. (Poster)

Sharples, S.A., Osachoff, N., and Whelan, P.J. A new method for detection of spontaneous rhythmic activity from ventral roots of the neonatal mouse isolated spinal cord. Society for Neuroscience, Washington, D.C., USA in November 2014. (Poster)