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Sleep-promoting effects of threonine link amino acid metabolism in Drosophila neuron to GABAergic control of sleep drive.

eLife | 2019

Emerging evidence indicates the role of amino acid metabolism in sleep regulation. Here we demonstrate sleep-promoting effects of dietary threonine (SPET) in Drosophila. Dietary threonine markedly increased daily sleep amount and decreased the latency to sleep onset in a dose-dependent manner. High levels of synaptic GABA or pharmacological activation of metabotropic GABA receptors (GABAB-R) suppressed SPET. By contrast, synaptic blockade of GABAergic neurons or transgenic depletion of GABAB-R in the ellipsoid body R2 neurons enhanced sleep drive non-additively with SPET. Dietary threonine reduced GABA levels, weakened metabotropic GABA responses in R2 neurons, and ameliorated memory deficits in plasticity mutants. Moreover, genetic elevation of neuronal threonine levels was sufficient for facilitating sleep onset. Taken together, these data define threonine as a physiologically relevant, sleep-promoting molecule that may intimately link neuronal metabolism of amino acids to GABAergic control of sleep drive via the neuronal substrate of sleep homeostasis.

Pubmed ID: 31313987 RIS Download

Research resources used in this publication

Associated grants

  • Agency: National Research Foundation of Korea, International
    Id: NRF-2017R1E1A2A02066965
  • Agency: National Research Foundation of Korea, International
    Id: NRF-2018R1A5A1024261
  • Agency: Suh Kyungbae Foundation, International
    Id: SUHF-17020101

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