State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518132, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; National Biomedical Imaging Center, Peking University, Beijing 100871, China; Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, Anhui, China.
State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; National Biomedical Imaging Center, Peking University, Beijing 100871, China.
Neuron. 2023 Apr 5;111(7):1118-1135.e5. doi: 10.1016/j.neuron.2022.12.034. Epub 2023 Jan 26.
The coincidence between conditioned stimulus (CS) and unconditioned stimulus (US) is essential for associative learning; however, the mechanism regulating the duration of this temporal window remains unclear. Here, we found that serotonin (5-HT) bi-directionally regulates the coincidence time window of olfactory learning in Drosophila and affects synaptic plasticity of Kenyon cells (KCs) in the mushroom body (MB). Utilizing GPCR-activation-based (GRAB) neurotransmitter sensors, we found that KC-released acetylcholine (ACh) activates a serotonergic dorsal paired medial (DPM) neuron, which in turn provides inhibitory feedback to KCs. Physiological stimuli induce spatially heterogeneous 5-HT signals, which proportionally gate the intrinsic coincidence time windows of different MB compartments. Artificially reducing or increasing the DPM neuron-released 5-HT shortens or prolongs the coincidence window, respectively. In a sequential trace conditioning paradigm, this serotonergic neuromodulation helps to bridge the CS-US temporal gap. Altogether, we report a model circuitry for perceiving the temporal coincidence and determining the causal relationship between environmental events.
条件刺激 (CS) 和非条件刺激 (US) 的同时出现对于联想学习至关重要；然而，调节这个时间窗口持续时间的机制仍不清楚。在这里，我们发现在果蝇中，血清素 (5-HT) 双向调节嗅觉学习的巧合时间窗口，并影响蘑菇体 (MB) 中感觉神经元的突触可塑性。利用基于 GPCR 激活的 (GRAB) 神经递质传感器，我们发现 KC 释放的乙酰胆碱 (ACh) 激活了一个血清素性背侧配对中脑 (DPM) 神经元，而 DPM 神经元反过来又向 KCs 提供抑制性反馈。生理刺激诱导空间异质的 5-HT 信号，这些信号成比例地调节不同 MB 隔室的固有巧合时间窗口。人为地减少或增加 DPM 神经元释放的 5-HT 分别缩短或延长了巧合窗口。在顺序痕迹条件反射范式中，这种血清素能神经调制有助于弥合 CS-US 时间间隙。总的来说，我们报告了一个用于感知时间巧合并确定环境事件之间因果关系的模型电路。
