Serotonin Signaling in Visual Processing Circuitry over Multiple Timescales

摘要 5-羟色胺能神经元广泛地支配果蝇的视觉系统， 然而，5-羟色胺信号在视觉处理中的作用尚不清楚。表达基因单个细胞的鉴定 视觉系统回路中的5-羟色胺受体将使我们能够确定5-羟色胺能 对视觉处理计算的调制。表达了五种遗传上不同的5-羟色胺受体 在整个视叶中，我们识别了特定的神经元和视觉处理路径 5-羟色胺神经调节。单细胞标记将5-羟色胺受体映射到特定的视觉处理 神经元：L2、L4、L5、T1、Lawf1和Lawf2。单极板单元2(L2)从 并表达5-羟色胺受体5-HT2B。钙成像证实增加了 L2和L1的基础钙对沐浴应用的5-羟色胺的反应。L1和L2 分别是启动和关闭通路中的一阶神经元，并且这两个信息流 馈入运动检测电路。L1神经元不表达5-羟色胺受体，表明间接 缝隙连接等机制使神经调节剂能够在没有受体的情况下影响细胞。我们 测试了5-羟色胺是否调节L2神经元的视觉反应，发现5-羟色胺增加了 视觉诱导的钙瞬变的大小。这表明，神经调节可能会调节突显 点燃路径中的特定视觉刺激。在这项工作中，我们测试了5-羟色胺信号和I 建议通过测量L2神经元的生理和转录变化来推进这些发现 伴随着5-羟色胺信号的慢性增加。综合起来，这些数据将使我们能够比较5-羟色胺 在多个时标上进行调制。此外，这些实验将揭示分子途径和 5-羟色胺信号级联下游的转录程序对长期治疗很重要 神经调节，并可能与人类的情绪提升有关。这项工作探索了分子 神经调节的机制，将有助于理解神经调节信号是如何 集成到感官回路中。

Abstract Serotonergic neurons extensively innervate the visual system of the fruit fly Drosophila melanogaster, yet the role of serotonin signaling in visual processing is unknown. Identification of individual cells expressing serotonin receptors in visual system circuits will allow us to determine the contribution of serotonergic modulation to visual processing computations. Five genetically distinct serotonin receptors are expressed throughout the optic lobe and we identified specific neurons and visual processing pathways targeted by serotonin neuromodulation. Single-cell labeling mapped serotonin receptors to specific visual processing neurons: L2, L4, L5, T1, Lawf1, and Lawf2. Lamina monopolar cell 2 (L2) receives direct input from photoreceptors and expresses the serotonin receptor 5-HT2B. Calcium imaging confirmed an increase in baseline calcium in response to bath-applied serotonin in L2 and its electrically coupled partner, L1. L1 and L2 are the first-order neurons in the light-ON and light-OFF pathways, respectively, and both information streams feed into motion detection circuits. L1 neurons do not express serotonin receptors, demonstrating that indirect mechanisms such as gap junctions enable neuromodulators to influence cells in the absence of receptors. We tested whether serotonin modulates visual responses in L2 neurons and found that serotonin increased the magnitude of visually induced calcium transients. This suggests that neuromodulation may regulate salience to specific visual stimuli in the light-OFF pathway. In this work we tested acute effects of serotonin signaling and I propose to advance these findings by measuring physiological and transcriptomic changes in L2 neurons following chronic increases in serotonin signaling. Together, these data will allow us to compare serotonin modulation over multiple timescales. Additionally, these experiments will reveal molecular pathways and transcriptional programs downstream of serotonin signaling cascades that are important for long-term neuromodulation and may be relevant to mood elevation in humans. This work explores the molecular mechanisms of neuromodulation and will contribute to the understanding of how neuromodulatory signaling is integrated into sensory circuits.