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bioRxiv · 10.1101/2025.09.16.676552

Dopamine promotes motor programs underlying substrate tunneling in larval Drosophila

MacLeod, J.·Ying, B. X.·Zwart, M. F.·Pulver, S. R.
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Abstract

Dopamine is a conserved biogenic amine with diverse neuromodulatory roles. Here we examine the role of dopamine in modulating larval Drosophila melanogaster motor programs underlying movement over and through substrates. First, we performed dual-color calcium imaging in tyrosine hydroxylase (TH)-expressing dopaminergic neurons and motor neurons to reveal cell-type specific recruitment patterns during fictive motor programs. Activity of select TH-neurons correlated strongly with fictive headsweeps as well as forward and backward locomotion. Next, bath applications of dopamine biased the isolated central nervous system towards fictive forward locomotion and inhibited fictive headsweeps. To probe whether these effects are recapitulated in intact animals, we optogenetically manipulated TH-neuron activity during surface crawling and tunneling. Optogenetic activation of TH-neurons with CsChrimson during crawling had no effect on headsweeps and slowed locomotor rhythms by increasing wave duration and decreasing wave frequency. Furthermore, posterior asymmetries, motor sequences characteristic of tunneling, were triggered. On the other hand, optogenetically inhibiting TH-neurons with GtACR1 had little effect on surface crawling. Underground, TH-neuron activation enhanced tunneling activity by increasing wave frequency, instead of duration, which increased overall time spent tunnelling, whereas inhibition decreased time spent tunneling. These results suggest that dopaminergic modulation of larval forward locomotion is dependent on sensorimotor context. We propose dopamine mediates a coordinated network effort to shift central pattern generators to promote tunneling-specific motor programs. New & NoteworthyHere, we find Drosophila larval dopaminergic neurons exhibit cell-type-specific activity in relation to fictive motor patterns. Furthermore, pharmacological and optogenetic manipulations of dopaminergic signaling acutely modifies locomotor output. Specifically, dopamine application promotes forward locomotion and inhibits headsweeps in isolated preparations, while optogenetically activating TH-neurons in freely behaving larvae mediates a shift from crawling to tunneling motor programs. This provides new insights into context-dependent dopaminergic modulation of locomotion in a genetically tractable invertebrate.

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MacLeod, J., Ying, B. X., Zwart, M. F., Pulver, S. R.. 2025-09-17. Dopamine promotes motor programs underlying substrate tunneling in larval Drosophila. https://doi.org/10.1101/2025.09.16.676552

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