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  • Title: Reciprocal modulation of 5-HT and octopamine regulates pumping via feedforward and feedback circuits in C. elegans.
    Author: Liu H, Qin LW, Li R, Zhang C, Al-Sheikh U, Wu ZX.
    Journal: Proc Natl Acad Sci U S A; 2019 Apr 02; 116(14):7107-7112. PubMed ID: 30872487.
    Abstract:
    Feeding is vital for animal survival and is tightly regulated by the endocrine and nervous systems. To study the mechanisms of humoral regulation of feeding behavior, we investigated serotonin (5-HT) and octopamine (OA) signaling in Caenorhabditis elegans, which uses pharyngeal pumping to ingest bacteria into the gut. We reveal that a cross-modulation mechanism between 5-HT and OA, which convey feeding and fasting signals, respectively, mainly functions in regulating the pumping and secretion of both neuromodulators via ADF/RIC/SIA feedforward neurocircuit (consisting of ADF, RIC, and SIA neurons) and ADF/RIC/AWB/ADF feedback neurocircuit (consisting of ADF, RIC, AWB, and ADF neurons) under conditions of food supply and food deprivation, respectively. Food supply stimulates food-sensing ADFs to release more 5-HT, which augments pumping via inhibiting OA secretion by RIC interneurons and, thus, alleviates pumping suppression by OA-activated SIA interneurons/motoneurons. In contrast, nutrient deprivation stimulates RICs to secrete OA, which suppresses pumping via activating SIAs and maintains basal pumping and 5-HT production activity through excitation of ADFs relayed by AWB sensory neurons. Notably, the feedforward and feedback circuits employ distinct modalities of neurosignal integration, namely, disinhibition and disexcitation, respectively.
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