Neuron-Astrocyte Interactions in Developmental Lead Exposure

摘要 血清素能神经元广泛支配果蝇果蝇的视觉系统， 然而，血清素信号在视觉处理中的作用尚不清楚。鉴定表达的单个细胞 视觉系统回路中的血清素受体将使我们能够确定血清素能的贡献 视觉处理计算的调制。表达五种遗传上不同的血清素受体 整个视叶，我们确定了特定的神经元和视觉处理通路 血清素神经调节。单细胞标记将血清素受体映射到特定的视觉处理 神经元：L2、L4、L5、T1、Lawf1 和 Lawf2。层板单极池 2 (L2) 接收来自 光感受器并表达血清素受体 5-HT2B。钙成像证实增加 L2 及其电耦合伙伴 L1 中对沐浴施加的血清素做出反应的基线钙。 L1 和 L2 分别是开灯和关灯通路中的一级神经元，并且两个信息流 馈入运动检测电路。 L1 神经元不表达血清素受体，这表明间接 间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 测试了血清素是否调节 L2 神经元的视觉反应，发现血清素增加了 视觉引起的钙瞬变的幅度。这表明神经调节可能调节显着性 关灯通路中的特定视觉刺激。在这项工作中，我们测试了血清素信号传导的急性影响和我 提议通过测量 L2 神经元的生理和转录组变化来推进这些发现 随着血清素信号的长期增加。总之，这些数据将使我们能够比较血清素 多个时间尺度上的调制。此外，这些实验将揭示分子途径和 血清素信号级联下游的转录程序对于长期而言很重要 神经调节，可能与人类情绪升高有关。这项工作探索了分子 神经调节机制，并将有助于理解神经调节信号传导是如何进行的 集成到感觉电路中。

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.