Dopamine is a conserved biogenic amine with diverse roles as a neuromodulator. In
Drosophila larvae, different types of dopaminergic neurons are present across the central nervous system (CNS), but the role(s) that dopamine plays in motor control in this system remain unclear. To address this problem, I used complementary techniques to either manipulate dopaminergic signalling or assess innate dopaminergic activity during locomotor activity. First, I used a genetically encoded calcium indicator to measure the output of central pattern generating (CPG) networks in isolated CNS preparations, then examined how pharmacological manipulations of dopamine signalling modulated the frequency of forward and backward fictive locomotion, as well as fictive head sweeping. Bath application of dopamine or the dopamine precursor L-Dopa, biased the intact isolated CNS towards forward fictive locomotion and inhibited fictive head sweeps. These effects showed evidence of activity state dependence and were antagonised by the non-specific dopamine receptor antagonist flupentixol. Next, I simultaneously imaged Ca²⁺ activity in motor neurons and in identified dopaminergic neurons during fictive locomotion using dual colour Ca²⁺ imaging. Dopaminergic neurons showed cell type specific patterns of recruitment, with some neurons preceding and others following, initiation of particular motor patterns. Finally, I expressed an optogenetic activator (CsChrimson) and inhibitor (GtACR1) in dopaminergic neurons and examined the effects of acutely raising and lowering activity in dopaminergic neurons. Optogenetic inhibition of dopamine neurons promoted head sweep motor programmes in both isolated CNS preparations and intact animals. Conversely, stimulation of dopaminergic neurons inhibited fictive head sweeps in freely moving animals and slowed the propagation of locomotor waves. These results suggest that dopamine differentially modulates distinct CPG modules underlying navigational motor programmes in the larval CNS. This work provides a foundation for future studies aimed at understanding the diversity of functional roles for dopamine neurons within locomotor networks.
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- 1 February 2027
Dopaminergic modulation of locomotor networks in larval
Drosophila melanogasterMacleod, J. (Author). 17 Jun 2022
Student thesis: Doctoral Thesis (PhD)