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Citation
Peng, J.J., Lin, S.H., Liu, Y.T., Lin, H.C., Li, T.N., Yao, C.K. (2019). A circuit-dependent ROS feedback loop mediates glutamate excitotoxicity to sculpt the Drosophila motor system.  eLife 8(): e47372.
FlyBase ID
FBrf0243117
Publication Type
Research paper
Abstract

Overproduction of reactive oxygen species (ROS) is known to mediate glutamate excitotoxicity in neurological diseases. However, how ROS burdens can influence neural circuit integrity remains unclear. Here, we investigate the impact of excitotoxicity induced by depletion of Drosophila Eaat1, an astrocytic glutamate transporter, on locomotor central pattern generator (CPG) activity, neuromuscular junction architecture, and motor function. We show that glutamate excitotoxicity triggers a circuit-dependent ROS feedback loop to sculpt the motor system. Excitotoxicity initially elevates ROS, thereby inactivating cholinergic interneurons and consequently changing CPG output activity to overexcite motor neurons and muscles. Remarkably, tonic motor neuron stimulation boosts muscular ROS, gradually dampening muscle contractility to feedback-enhance ROS accumulation in the CPG circuit and subsequently exacerbate circuit dysfunction. Ultimately, excess premotor excitation of motor neurons promotes ROS-activated stress signaling that alters neuromuscular junction architecture. Collectively, our results reveal that excitotoxicity-induced ROS can perturb motor system integrity through a circuit-dependent mechanism.

PubMed ID
PubMed Central ID
PMC6682402 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Location data for Eaat1[hypo] allele.
Yao, 2019.11.13, Location data for Eaat1[hypo] allele. [FBrf0244006]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    eLife
    Title
    eLife
    ISBN/ISSN
    2050-084X
    Data From Reference