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Dissertation
Role of dopaminergic descending neurons in the control of locomotion in Drosophila
Doctor of Philosophy (Ph.D.), Drexel University
May 2025
DOI:
https://doi.org/10.17918/00011054
Abstract
Dopaminergic neurons (DANs) play a pivotal role in regulating a wide range of functions, including reward processing, learning, and locomotion. These roles are highly conserved across species, from invertebrates like Drosophila to mammals. There is one population of DANs with cell bodies in the hypothalamus and axons projecting to the spinal cord (referred to as dopaminergic descending neurons or DADNs). Pharmacological manipulations show that DADNs play a critical role in motor control. However, due to a lack of in vivo research, the specifics of how these neurons modulate the spinal motor circuits, as well as the dynamics of dopamine and dopamine receptors during behavior, remain poorly understood. Therefore, there is an urgent need to characterize the role of these neurons in vivo. We chose to address this problem in Drosophila melanogaster. There are only two DADNs, which makes understanding their role in motor control tractable. In this study, we aimed to 1) test whether DADNs' activity is related to leg movements or specific locomotor parameters; 2) assess how perturbations in these neurons impact behavior; and 3) determine the mechanism of dopamine action in the VNC. I performed electrophysiological recordings on DADNs during optogenetic manipulation while simultaneously measuring behavioral changes and introducing mutations in dopamine receptors to assess the resulting alterations in behavior. My findings indicate that DADN activity exhibits a strong relationship with leg movements but a weak relationship with locomotion; furthermore, both activating and inactivating these neurons increases behavioral output, and this effect is modulated by the inhibitory dopamine receptor Dop2R. This research provides valuable insights into the mechanism by which DADNs modulate motor circuits at cellular and network levels, bringing an advanced understanding of their role in motor control during locomotion, which is a challenge in other animal models.
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Details
- Title
- Role of dopaminergic descending neurons in the control of locomotion in Drosophila
- Creators
- Ninghan Wang
- Contributors
- Vikas Bhandawat (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xv, 130 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991022058734304721