The nematode C. elegans is a multicellular model organism to study the neuronal-basis of behaviour. C. elegans demonstrates an innate response to swim towards the cathode in the presence of a DC electric field(EF), a behaviour known as “electrotaxis”. We examined mutants affecting sensory and dopaminergic neurons and found that these mutants moved with reduced speed with intermittent pauses, abnormal turning, and slower body bend. A similar phenotype was observed in worms treated with neurotoxins 6-OHDA, MPTP and rotenone. Pre-exposing worms to a known neuroprotective compound acetaminophen could suppress the effects of neurotoxin on movement.
Further, this study demonstrates that dopamine and the D2-type dopamine receptor are necessary to modulate electrotactic movements in worms. A reduction in extracellular dopamine leads to a significant increase in the swimming speed as judged by the analysis of bas-1(dopa decarboxylase) and cat-1(VMAT) mutants. The dopamine transporter dat-1 acts genetically downstream of bas-1 and cat-1 since dat-1 mutants efficiently suppress bas-1 and cat-1 phenotypes. We also found that DOP-3(D2-type receptor) acts as the sole receptor for dopamine-mediated regulation of electrotaxis. Interestingly, we found that prolonged exposure to EF resulted in a gradual decline in the swimming speed such that animals were 40% slower at the end of ten minutes exercise period. This change is mediated by DOP-3 since dop-3 mutants continue to swim at the initial speed and don’t slow down. This conclusion is supported by the analysis of animals treated with Heloperidol(D2 antagonist) and SKF38393(D1 agonist). Overall, our work demonstrates that D2 receptor-mediated neuronal signalling is required to restrict muscle activity not only during the initial phase of electrotaxis swimming but also for the entire duration of the assay. We suggest that such a role of dopamine signalling might serve as an important and conserved mechanism to limit muscle overuse during prolonged physical exercise. / Thesis / Doctor of Science (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/18697 |
| Date | January 2016 |
| Creators | Salam, Sangeena Devi |
| Contributors | Gupta, Bhagwati, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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