Dopamine receptor DOP-1 engages a sleep pathway to modulate swimming in C. elegans

Abstract

Summary Animals require robust yet flexible programs to support locomotion. Here we report a pathway that connects the D1-like dopamine receptor DOP-1 with a sleep mechanism to modulate swimming in C. elegans . We show that DOP-1 plays a negative role in sustaining swimming behavior. By contrast, a pathway through the D2-like dopamine receptor DOP-3 negatively regulates the initiation of swimming, but its impact fades quickly over a few minutes. We find that DOP-1 and the GPCR kinase (G-protein-coupled receptor kinase-2) function in the sleep interneuron RIS, where DOP-1 modulates the secretion of a sleep neuropeptide FLP-11. We further show that DOP-1 and FLP-11 act in the same pathway to modulate swimming. Together, these results delineate a functional connection between a dopamine receptor and a sleep program to regulate swimming in C. elegans . The temporal transition between DOP-3 and DOP-1 pathways highlights the dynamic nature of neuromodulation for rhythmic movements that persist over time.

The neuropeptidergic connectome ofC. elegans

“…In addition, the neuropeptide connectome contains 6 neurons whose neuropeptide degree is higher than any of the synaptic rich club (degree > 490). Three of these neurons (PVT and the pair of AVK neurons) are specialized peptidergic neurons that express no classical neurotransmitter or monoamine and have been linked to arousal and sleep-like behaviors 14, 92, 93 . Specialized neuropeptidergic neurons have also been described in other organisms, and in mice they have been linked to global behaviors such as fear 94 .…”

Using a Caenorhabditis elegans Parkinson’s Disease Model to Assess Disease Progression and Therapy Efficiency

“…The strain used here has α-synuclein being expressed in the body wall muscles and, therefore, it raises the question as to how exposure to Levodopa would recover the mobility defect in muscles that are not directly innervated by dopaminergic neurons. In C. elegans , dopamine receptors can be found throughout the nematode nervous system, and a connection has been shown between dopamine, motor circuitry, and behaviors including locomotion [ 95 , 96 , 97 ]. Indeed, two key dopamine receptors, D1- and D2-like receptors (DOP-1 and DOP-3, respectively in C. elegans ), are present in cholinergic and GABAergic motor neurons, which are key in the control of worm mobility [ 72 , 97 ].…”

Loss of physical contact in space alters the dopamine system in C. elegans

“…While there are at least 5 dopamine receptors in C. elegans, the D1-like receptor (D1R) DOP-1 and the D2R DOP-3, expressed in ventral cord motor neurons which innervate the body wall muscles, control locomotion (Han et al, 2017;Sawin et al, 2000). DOP-1 and DOP-3 antagonize each other in the same neuronal cells (Allen et al, 2011;Chase et al, 2004) with DOP-3 controlling the slowing response and contributing to spatial pattern selectivity, regulation of olfactory sensitivity, and the swimming behavior (Allen et al, 2011;Chase et al, 2004;Ezak and Ferkey, 2010;Han et al, 2017;Xu et al, 2021). DA also regulates C. elegans body length (Nagashima et al, 2016) and synapses onto motoneurons, plausibly linking mG induced decreases in body length and impaired muscular performance (Higashibata et al, 2016).…”