Metabolic control of daily locomotor activity mediated by tachykinin in Drosophila

Lee, Sang Hyuk; Cho, Eunjoo; Yoon, Sung Eun; Kim, Youngjoon; Kim, Eun Young

doi:10.1038/s42003-021-02219-6

Cited by 13 publications

(8 citation statements)

References 97 publications

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“…Such a robust strategy is unlikely to rely on a single perturbation that could be countered by simple evolutionary changes in the host. An increase in locomotion can be achieved in many ways and is the likely output of many different behavioral circuits ( Bidaye et al, 2020 ; Cavanaugh et al, 2014 ; Lee et al, 2021 ), so it would be unsurprising to find that multiple host circuits are targeted, including others yet to be discovered. Nevertheless, our study has identified a host pathway that likely mediates the predominant effects of the zombie fly summiting manipulation.…”

Section: Discussionmentioning

confidence: 99%

Neural mechanisms of parasite-induced summiting behavior in ‘zombie’ Drosophila

Elya

Lavrentovich

Lee

et al. 2023

eLife

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For at least two centuries, scientists have been enthralled by the 'zombie' behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the recently established Entomophthora muscae-Drosophila melanogaster 'zombie fly' system to reveal the molecular and cellular underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a new, high-throughput behavior assay to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), who are solely responsible for juvenile hormone (JH) synthesis and release. Summiting is a fleeting phenomenon, posing a challenge for physiological and biochemical experiments requiring tissue from summiting flies. We addressed this with a machine learning classifier to identify summiting animals in real time. PI-CA neurons and CA appear to be intact in summiting animals, despite E. muscae cells invading the host brain, particularly in the superior medial protocerebrum (SMP), the neuropil that contains DN1p axons and PI-CA dendrites. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the fly's hemolymph, activating the neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.

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Section: Discussionmentioning

confidence: 99%

Neural mechanisms of parasite-induced summiting behavior in ‘zombie’ Drosophila

Elya

Lavrentovich

Lee

et al. 2023

eLife

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“…In male flies, one set of TK neurons (LPP1b) express the male splice form of the transcription factor fruitless (Fru M ), and probably acetylcholine (Ach), and regulate levels of aggression via TkR86C [ 100 ]. A small group of TK neurons act on TkR86C, expressed by specific clock neurons, to modulate daily locomotor activity [ 157 ]. Other subsets of the TK neurons modulate pheromone sensing and regulate activity in the insulin-producing cells (IPCs) [ 103 , 104 , 158 , 159 ].…”

Section: Examples Of Peptidergic Regulation Of State-dependent Behavi...mentioning

confidence: 99%

Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions

Nässel

Zandawala

2022

Open Biol.

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Plasticity in animal behaviour relies on the ability to integrate external and internal cues from the changing environment and hence modulate activity in synaptic circuits of the brain. This context-dependent neuromodulation is largely based on non-synaptic signalling with neuropeptides. Here, we describe select peptidergic systems in the Drosophila brain that act at different levels of a hierarchy to modulate behaviour and associated physiology. These systems modulate circuits in brain regions, such as the central complex and the mushroom bodies, which supervise specific behaviours. At the top level of the hierarchy there are small numbers of large peptidergic neurons that arborize widely in multiple areas of the brain to orchestrate or modulate global activity in a state and context-dependent manner. At the bottom level local peptidergic neurons provide executive neuromodulation of sensory gain and intrinsically in restricted parts of specific neuronal circuits. The orchestrating neurons receive interoceptive signals that mediate energy and sleep homeostasis, metabolic state and circadian timing, as well as external cues that affect food search, aggression or mating. Some of these cues can be triggers of conflicting behaviours such as mating versus aggression, or sleep versus feeding, and peptidergic neurons participate in circuits, enabling behaviour choices and switches.

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“…Sensory receptors in animals transform external visual ( Creamer et al, 2018 ), olfactory ( Tao et al, 2020 ), and thermal ( Soto-Padilla et al, 2018 ) stimuli into internal information, which the central nervous system converts into an appropriate motor output ( Gowda et al, 2021 ). In Drosophila , locomotion is affected by alteration of the internal metabolic status caused by time-restricted feeding ( Villanueva et al, 2019 ), or by high sugar ( Lee et al, 2021 ), high fat ( Huang et al, 2020 ), or high salt ( Xie et al, 2019 ) levels. The relatively simple and well-characterized central nervous system of Drosophila makes it an excellent model for studying locomotion ( Scheffer et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The prominin-like Gene Expressed in a Subset of Dopaminergic Neurons Regulates Locomotion in Drosophila

Ryu

Manivannan

Yeom

et al. 2022

Molecules and Cells

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CD133, also known as prominin-1, was first identified as a biomarker of mammalian cancer and neural stem cells. Previous studies have shown that the prominin-like (promL) gene, an orthologue of mammalian CD133 in Drosophila, plays a role in glucose and lipid metabolism, body growth, and longevity. Because locomotion is required for food sourcing and ultimately the regulation of metabolism, we examined the function of promL in Drosophila locomotion. Both promL mutants and pan-neuronal promL inhibition flies displayed reduced spontaneous locomotor activity. As dopamine is known to modulate locomotion, we also examined the effects of promL inhibition on the dopamine concentration and mRNA expression levels of tyrosine hydroxylase (TH) and DOPA decarboxylase (Ddc), the enzymes responsible for dopamine biosynthesis, in the heads of flies. Compared with those in control flies, the levels of dopamine and the mRNAs encoding TH and Ddc were lower in promL mutant and pan-neuronal promL inhibition flies. In addition, an immunostaining analysis revealed that, compared with control flies, promL mutant and panneuronal promL inhibition flies had lower levels of the TH protein in protocerebral anterior medial (PAM) neurons, a subset of dopaminergic neurons. Inhibition of promL in these PAM neurons reduced the locomotor activity of the flies. Overall, these findings indicate that promL expressed in PAM dopaminergic neurons regulates locomotion by controlling dopamine synthesis in Drosophila.

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Metabolic control of daily locomotor activity mediated by tachykinin in Drosophila

Cited by 13 publications

References 97 publications

Neural mechanisms of parasite-induced summiting behavior in ‘zombie’ Drosophila

Neural mechanisms of parasite-induced summiting behavior in ‘zombie’ Drosophila

Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions

The prominin-like Gene Expressed in a Subset of Dopaminergic Neurons Regulates Locomotion in Drosophila

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