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  1. This art work is a meme collection diagraming the relationship of the substantia nigra (SN), dopamine D1 and D2 pathways, and movement signals to the striatum as well as the comparison of normal functioning to that of normal functioning D1 pathways and those with lesions resulting in Parkinson’s Disease. Parkinson’s Disease is a well-known disease that results in poor motor control due to many factors, one of which is the breakdown or death of neurons in the brain that will, admittedly, be grossly oversimplified in this project.
    Before going into diagraming the individual memes themselves, it is important to explain some newer ideas regarding the substantia nigra pars compacta (SNpc) and theories behind movement. Historically, it was believed that the SNpc was directly implicated in the beginnings of motor movement and control. Newer theories suggest that rather than directly causing movement, the SNpc is more indirectly implicated and creates bodily movement through signals sent to the striatum. (Pioli et al, 2008) A gross simplification would be that it is presently believed the SNpc acts perhaps more similarly to the brake and gas of a motor vehicle versus previously it was believed to be the actual throttle body itself.
    In the first frame, the diagram shows a popular meme of SpongeBob Squarepants citing his desire to get up from a chair and depart, a common action many humans engage in. This begins the neuron firing process in the substantia nigra.
    In the second and third frames the relationships of the D1 and D2 receptors are discussed. In the second meme, it is a picture of a club with a DJ. The DJ is shown playing music and getting club attendees to dance. This outlines how the SN projects dopamine to the D1 pathway, exciting the receptors and stimulating activity or acting as the gas pedal of a car. In the third meme, a picture of a napping contest is shown with a referee observing the participants napping. This diagrams how when the SN projects dopamine along the D2 pathway, it results in inactivation of the pathway. (Lew & Yeung, 2014)
    In Parkinson’s Disease, we see dysfunction specifically in the D1 pathway of the SN. The fourth and fifth memes describe the difference between intact and lesioned pathways. Recent research in rats was found that when the D1 pathway of the SN was purposely lesioned, the rats showed symptoms similar to Parkinson’s Disease, specifically motor dysfunction and poor motor control. (Pelosi, Girault, & Hervé, 2015) We see in the fourth meme a smooth road that is obviously of a good condition to operate a vehicle on, indicative of the signals being transmitted along an intact SN D1 pathway. In the fifth meme, we see a road that has been damaged and covered by flood water, a road difficult to pass even by the most durable of vehicles. Such a road would surely make for an uncomfortable drive that would also cause damage to the vehicle over time. In a degraded SN D1 pathway, electrical signaling would operate similarly and it is expected signal degradation would be present. (Lew & Yeung, 2014)
    In the sixth meme, a picture of a passed out goat is displayed to show dead D1 receptors. In Parkinson’s Disease, the SN D1 pathways become degraded due to the death of D1 receptors in that part of the brain. (Tansey & Goldberg, 2010)
    In the last two memes we see the comparison of a racing car smoothing coming up the track and another car that has spun out of control. In a normally operating SN D1 pathway, electrical signals arrive at the striatum intact and carrying the messages indicated and this is indicated by the race car arriving as it should or movement instructions to the body that result in controlled movements. In a lesioned SN D1 pathway, we expect that the electrical signals would not arrive to the striatum intact and this would result in jerky and uncoordinated motor control. (Pelosi, Girault, & Hervé, 2015)
    Certainly, many complex factors and theories exist for the pathogenesis of Parkinson’s Disease and the disease impacts many people in differing ways. Research into the SN D1 pathway is producing research for D1 agonists that only focus on the D1 pathway to help reduce the death of cells along that pathway and offset symptoms. (Fox & Lang, 2010)
     
    References
    Fox, S., & Lang, A. E. (2010). Chapter 15 – Therapy of the Motor Features of Parkinson’s Disease. In Blue Books of Neurology (Vol. 34, pp. 252—272). Butterworth-Heinemann. doi: https://doi.org/10.1016/B978-1-4160-6641-5.00015-5
    Lew, M. F., & Yeung, Y. (2014). Reference Module in Biomedical Sciences. doi: https://doi.org/10.1016/B978-0-12-801238-3.00146-X
    Pelosi, A., Girault, J. A., & Hervé, D. (2015). Unilateral Lesion of Dopamine Neurons Induces Grooming Asymmetry in the Mouse. PloS one, 10(9), e0137185. doi:10.1371/journal.pone.0137185
    Pioli, E.Y.; Meissner, W.; Sohr, R.; Gross, C.E.; Bezard, E.; Bioulac, B.H. (2008). “Differential behavioral effects of partial bilateral lesions of ventral tegmental area or substantia nigra pars compacta in rats”. Neuroscience. 153 (4): 1213—24. doi:10.1016/j.neuroscience.2008.01.084
    Tansey, M. G., & Goldberg, M. S. (2010). Neuroinflammation in Parkinson’s disease: Its role in neuronal death and implications for therapeutic intervention. Neurobiology of Disease, 37(3), 510-518. doi:10.1016/j.nbd.2009.11.004

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