Whelan, Patrick J.Mayr, Kyle Andrew2018-09-172018-09-172018-09-06Mayr, K. A. (2018). Dopaminergic modulation of spinal circuits for walking in the adult mouse (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32925http://hdl.handle.net/1880/107749Walking is a stereotyped rhythmic behavior that consists of alternating contractions of flexor and extensor muscles, as well as the left and right hindlimbs. The basic rhythmic pattern underlying locomotion is generated by a central pattern generator network within the lumbar spinal cord. The role of many neurotransmitters and modulators have been studied extensively, but dopamine’s (DA) role in modulating movement at the level of the lumbar spinal cord, is still not fully understood, especially in adult mice. The decerebrate mouse preparation allows us to examine modulation of stepping behaviour in adult mice with reduced descending inputs to the spinal cord, while intrathecally manipulating the lumbar spinal cord. Locomotor activity was measured by recording weight bearing during locomotion and electromyograms (EMG) from the flexor (tibialis anterior) and extensor (gastrocnemius) muscles of the hindlimbs. Our results show that intrathecal application of DA at the lumbar spinal cord increased the duration of locomotor bouts. Intrathecal DA led to an increase in weight bearing, suggesting that DA may promote extensor biased walking. Furthermore, addition of D1-like agonists augmented weight bearing in the decerebrate animal, but not as much as DA alone. Using intact animals intrathecally injected with either DA, or DA antagonists we selectively activated or blocked DA receptor subtypes of the spinal cord. Using the open field test and ladder rung, we quantified the amount of activity, type of activity and scored the skilled steps during locomotion. Our findings show that DA decreased the amount of locomotor activity in the open field but did not have a significant effect on the ladder rung step score. Furthermore, we found that D1-like antagonists reduced locomotor activity (distance, velocity and bouts) while D2-like antagonists did not have a significant impact on open field activity, though there was an increase in errors while crossing the ladder rung. This thesis provides insight into the DAergic contribution to the modulation in adult mouse locomotion and bridges the gap from previous neonatal animal work. It shows that DA can have differential effects dependant on the state of the animal and provides a foundation for future work on DA neuromodulation.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.DopamineDecerebratelocomotioncentral pattern generatorsteppingspinal cordmonoamineNeurosciencemaster thesis10.11575/PRISM/32925