Dop1R1, a type 1 dopaminergic receptor expressed in Mushroom Bodies, modulates Drosophila larval locomotion

Silva, Bryon; Hidalgo, Sergio; Campusano, Jorge M.

doi:10.1371/journal.pone.0229671

Cited by 9 publications

(10 citation statements)

References 59 publications

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“…Such behaviour would correspond to the behaviour of adult flies and mice after cocaine administration [56–58, 60], and to what was observed in highly active flies upon activation of dopamine neurons [61]. Our results are also in line with one of the very few studies that link dopamine function with locomotion in larvae: a transgenic knockdown of the dopamine receptor Dop1R1, one of the two Drosophila homologs of the vertebrate D1-type dopamine receptors, was reported to increase locomotion in larvae [63]. Our experimental treatment, in contrast, acutely increased dopamine signalling, leading to reduced forward locomotion.…”

Section: Discussionsupporting

confidence: 88%

“…Interestingly, the effects of the Dop1R1-knockdown were also observed when it occurred locally only in the mushroom body, one of the central brain regions in insects [63]. The dopamine neurons innervating the mushroom body play a crucial role in signalling reward or punishment information in associative learning [29,[64][65][66][67][68].…”

Section: Activation Of Dopamine Neurons Makes Larvae Stop and Turnmentioning

confidence: 99%

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High-resolution analysis of individualDrosophila melanogasterlarvae within groups uncovers inter- and intra-individual variability in locomotion and its neurogenetic modulation

Thane

Paisios

Stöter

et al. 2022

Preprint

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Neuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its numerically simple brain and neuromuscular system and its genetic accessibility, the larva of the fruit fly Drosophila melanogaster is an established model to study these processes at tractable levels of complexity. However, although the faculty of locomotion clearly pertains to the individual animal, present studies of locomotion in larval Drosophila mostly use group assays and measurements aggregated across individual animals. The alternative is to measure animals one at a time, an extravagance for larger-scale analyses. In principle or in practice, this in particular rules out grasping the inter- and intra-individual variability in locomotion and its genetic and neuronal determinants. Here we present the IMBA (Individual Maggot Behaviour Analyser) for tracking and analysing the behaviour of individual larvae within groups. Using a combination of computational modelling and statistical approaches, the IMBA reliably resolves individual identity across collisions. It does not require specific hardware and can therefore be used in non-expert labs. We take advantage of the IMBA first to systematically describe the inter- and intra-individual variability in free, unconstrained locomotion in wild-type animals. We then report the discovery of a novel, complex locomotion phenotype of a mutant lacking an adhesion-type GPCR. The IMBA further allows us to determine, at the level of individual animals, the modulation of locomotion across repeated activations of dopamine neurons. Strikingly, IMBA can also be used to analyse 'silly walks', that is patterns of locomotion it was not originally designed to investigate. This is shown for the transient backward locomotion induced by brief optogenetic activation of the brain-descending 'mooncrawler' neurons, and the variability in this behaviour. Thus, the IMBA is an easy-to-use toolbox allowing an unprecedentedly rich view of the behaviour and behavioural variability of individual Drosophila larvae, with utility in multiple biomedical research contexts.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Activation Of Dopamine Neurons Makes Larvae Stop and Turnmentioning

confidence: 99%

High-resolution analysis of individualDrosophila melanogasterlarvae within groups uncovers inter- and intra-individual variability in locomotion and its neurogenetic modulation

Thane

Paisios

Stöter

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Such behaviour would correspond to the behaviour of adult flies and mice after cocaine administration [64][65][66]68], and to what was observed in highly active flies upon activation of dopamine neurons [69]. Our results are also in line with one of the very few studies that link dopamine function with locomotion in larvae: a transgenic knockdown of the dopamine receptor Dop1R1, one of the two Drosophila homologues of the vertebrate D1-type dopamine receptors, was reported to increase locomotion in larvae [71]. Our experimental treatment, in contrast, acutely increased dopamine signalling, leading to reduced forward locomotion.…”

Section: Activation Of Dopamine Neurons Makes Larvae Stop and Turnsupporting

confidence: 89%

“…Interestingly, the effects of the Dop1R1-knockdown were also observed when it occurred locally only in the mushroom body, one of the central brain regions in insects [71]. The dopamine neurons innervating the mushroom body play a crucial role in signalling reward or punishment information in associative learning [30,[72][73][74][75][76].…”

Section: Activation Of Dopamine Neurons Makes Larvae Stop and Turnmentioning

confidence: 99%

High-resolution analysis of individual Drosophila melanogaster larvae uncovers individual variability in locomotion and its neurogenetic modulation

et al. 2023

View full text Add to dashboard Cite

Neuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its simple brain and genetic accessibility, the larva of the fruit fly Drosophila melanogaster allows one to study these processes at tractable levels of complexity. However, although the faculty of locomotion clearly pertains to the individual, most studies of locomotion in larvae use measurements aggregated across animals, or animals tested one by one, an extravagance for larger-scale analyses. This prevents grasping the inter- and intra-individual variability in locomotion and its neurogenetic determinants. Here, we present the IMBA (individual maggot behaviour analyser) for analysing the behaviour of individual larvae within groups, reliably resolving individual identity across collisions. We use the IMBA to systematically describe the inter- and intra-individual variability in locomotion of wild-type animals, and how the variability is reduced by associative learning. We then report a novel locomotion phenotype of an adhesion GPCR mutant. We further investigated the modulation of locomotion across repeated activations of dopamine neurons in individual animals, and the transient backward locomotion induced by brief optogenetic activation of the brain-descending ‘mooncrawler’ neurons. In summary, the IMBA is an easy-to-use toolbox allowing an unprecedentedly rich view of the behaviour and its variability of individual larvae, with utility in multiple biomedical research contexts.

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“…Two strains generated either by insertion of transposable elements or gene inversion showed impaired responses to conditioning stimuli, rescued by reinstating dDA1 expression [ 37 ]. In contrast, reduction of dDA1 expression by RNA interference resulted in increased larval locomotion, [ 38 ] whereas a similar approach significantly reduced motor activity in adult flies [ 39 ]. Despite these phenotypic differences, mouse and Drosophila models collectively appear to support an essential role for DRD1 in motor development.…”

Section: Discussionmentioning

confidence: 99%

Loss-of-Function Variants in DRD1 in Infantile Parkinsonism-Dystonia

Reid¹,

Steel

Nair

et al. 2023

Cells

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The human dopaminergic system is vital for a broad range of neurological processes, including the control of voluntary movement. Here we report a proband presenting with clinical features of dopamine deficiency: severe infantile parkinsonism-dystonia, characterised by frequent oculogyric crises, dysautonomia and global neurodevelopmental impairment. CSF neurotransmitter analysis was unexpectedly normal. Triome whole-genome sequencing revealed a homozygous variant (c.110C>A, (p.T37K)) in DRD1, encoding the most abundant dopamine receptor (D1) in the central nervous system, most highly expressed in the striatum. This variant was absent from gnomAD, with a CADD score of 27.5. Using an in vitro heterologous expression system, we determined that DRD1-T37K results in loss of protein function. Structure-function modelling studies predicted reduced substrate binding, which was confirmed in vitro. Exposure of mutant protein to the selective D1 agonist Chloro APB resulted in significantly reduced cyclic AMP levels. Numerous D1 agonists failed to rescue the cellular defect, reflected clinically in the patient, who had no benefit from dopaminergic therapy. Our study identifies DRD1 as a new disease-associated gene, suggesting a crucial role for the D1 receptor in motor control.

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Dop1R1, a type 1 dopaminergic receptor expressed in Mushroom Bodies, modulates Drosophila larval locomotion

Cited by 9 publications

References 59 publications

High-resolution analysis of individualDrosophila melanogasterlarvae within groups uncovers inter- and intra-individual variability in locomotion and its neurogenetic modulation

High-resolution analysis of individualDrosophila melanogasterlarvae within groups uncovers inter- and intra-individual variability in locomotion and its neurogenetic modulation

High-resolution analysis of individual Drosophila melanogaster larvae uncovers individual variability in locomotion and its neurogenetic modulation

Loss-of-Function Variants in DRD1 in Infantile Parkinsonism-Dystonia

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