探討線蟲受粒線體損傷引發之細菌迴避行為的血清素神經迴路

Abstract

學習幫助動物更好地適應環境變化。學習的過程中，動物改變神經迴路的結構或功能，進而調控其行為。血清素(serotonin)是一種神經調節劑，高度保留在不同物種，調控動物的內在狀態，如醒覺、焦慮以及恐懼。然而，目前研究並未詳細指出血清素迴路與行為可塑性的關聯。本研究利用秀麗隱桿線蟲，探討內在生理狀況如何重塑血清素迴路。當正常生理機制遭受干擾，如粒線體的損傷，線蟲會調整其行為以適應環境。線蟲可連結粒線體受損的事件與其當下所攝取食物的訊息，並改變其先天對於無害細菌的喜好，進而產生厭惡行為。此行為具有聯想記憶的數個特徵，如專一性。我們的研究指出粒線體的損傷增加血清素於NSM之合成與釋放，且極可能透過其下游之中間神經元RIB表現的G蛋白偶聯受體SER-4，調控線蟲的行為。NSM神經元可能具有監控線蟲消化道的功能，暗示其偵測內在生理狀況的可能性。未來我們將著重於此聯想學習中，NSM與RIB神經元活性的改變，與個體線蟲如何衍生運動策略。此研究使我們對於內在狀態相關之學習行為與血清素的關聯有了更進一步的了解。

Internal physiological states shape behaviors evoked by sensory cues by changing the structure or function of neuronal circuits. Serotonin is a conserved neuromodulatory signal that has been proposed to report internal states of the animal, such as arousal, anxiety or fear, but how serotonergic circuits link internal states to behavioral plasticity remains largely unclear. Here, we characterize a serotonin circuit that modulates aversive associative learning triggered by mitochondrial insult in the nematode Caenorhabditis elegans. Innate preference of C. elegans for nutritious bacteria can switch to aversion by concurrent disruption of mitochondrial functions. This learned bacterial aversion displays core features of associated aversive memory including specificity to the conditioned stimuli. We found that serotonin is required for conditioned bacterial aversion, and it enhances bacterial avoidance in the presence of mild mitochondrial disruption. Mitochondrial injury likely increases serotonin synthesis and secretion from the NSM modulatory neurons, which targets the interneurons RIB that express the G-protein coupled serotonergic receptor SER-4. NSM is hypothesized to monitor signals from the digestive tract of C. elegans, raising the possibility that it is an interoceptive neuron for reporting the physiological states of the animal. In the future, we will investigate how serotonergic signaling reshapes circuit functions and organizes the animals’ locomotion strategies to promote avoidance behavior. Our findings provide insight into the neuromodulatory mechanisms underlying behavioral plasticity triggered by changes of the internal states.