Dopaminergic control of spinal circuits

My PhD work was conducted in the Lab of Dr. Patrick Whelan at the University of Calgary’s Hotchkiss Brain Institute.

Whelan Lab

University of Calgary

Visit the Lab website to learn more about ongoing work in the Whelan Lab.

The primary focus of my PhD work was to understand the adaptability of neural networks in the spinal cord that lead to the generation of diverse rhythmic outputs that could manifest as different locomotor patterns, or gaits.

Neuromodulators serve as one means to accomplish this. I focused on dopamine in particular which is well known for its role in the control of movement through action in the brain; however, its role in the control of spinal networks was relatively less understood. I discovered that dopamine has the capacity to elicit a diverse array of rhythmic activities from lumbar networks of the newborn mouse in vitro. I later found out that this capacity was not unique to dopamine, but also serotonin and may therefore a property of spinal networks.

I pursued three primary lines of inquiry during my PhD:

State-dependent neuromodulation
Dynamics and state-dependence of dopamine receptor actions
Intrinsic mechanisms governing pattern switching

Tools

In vitro preparations

Electrophysiology

Immunohistochemistry

Collaborations

This work was enriched through several collaborations.

Nicole Burma, PhD

University of Calgary

Glen Baker, PhD

University of Alberta

Ying Zhang, PhD

Dalhousie University

Stefan Clemens, PhD

East Carolina University

Gennady Cymbalyuk, PhD

Georgia State University

Outputs

Research Articles

Sharples, S.A., Parker, J., Vargas, A., Milla-Cruz, J.J., Lognon, A.P., Cheng, N., Young, L., Shonak, A., Cymbalyuk, G., and Whelan, P.J. (2022). Contributions of h- and Na⁺/K⁺ pump currents to the generation of episodic and continuous rhythmic activities. Frontiers in Cellular Neuroscience. 15: 715427. DOI:10.3389/fncel.2021.715427.

Sharples, S.A., Burma, N.E., Borowska-Fielding, J., Kwok, C.H.T., Eaton, S.E.A, Baker, G., Jean-Xavier, C., Zhang, Y., Trang, T., and Whelan, P.J. (2020). A dynamic role for dopamine receptors in the regulation of mammalian spinal motor networks. Scientific Reports. 10: 16429. DOI: 10.1038/s41598-020-73230-w

Sharples, S.A. (2017). Dopamine pumping up spinal locomotor network function. Journal of Neuroscience. 37 (12): 3103-3105. DOI: 10.1523/JNEUROSCI.0019-17.2017.

Sharples, S.A. and Whelan, P.J.(2017). Modulation of rhythmic activity in mammalian spinal networks is dependent on excitability state. eNeuro. 4 (1): ENEURO 0368-16.2017. DOI:10.1523/ENEURO.0368-16.2017.

Sharples, S.A., Humphreys, J.M., Jensen, A.M., Dhoopar, S., Delaloye, N., Clemens, S., and Whelan, P.J. (2015).Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord. Journal of Neurophysiology. 113 (7): 2500-2510. DOI: 10.1152/jn.00849.2014. (IF: 2.9, citations: 33).

Sharples, S.A., Koblinger K, Humphreys J.M. and Whelan P.J. (2014). Dopamine: a parallel pathway for the modulation of spinal locomotor networks. Frontiers in Neural Circuits 8 (55). DOI: 10.3389/fncir.2014.00055.