Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning.

Jianzhi Zeng, Xuelin Li, Renzimo Zhang, Mingyue Lv, Yipan Wang, Ke Tan, Xiju Xia, Jinxia Wan, Miao Jing, Xiuning Zhang, Yu Li, Yang Yang, Liang Wang, Jun Chu, Yan Li, Yulong Li

Neuron 2023 Apr 05

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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. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Jianzhi Zeng, Xuelin Li, Renzimo Zhang, Mingyue Lv, Yipan Wang, Ke Tan, Xiju Xia, Jinxia Wan, Miao Jing, Xiuning Zhang, Yu Li, Yang Yang, Liang Wang, Jun Chu, Yan Li, Yulong Li. Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning. Neuron. 2023 Apr 05;111(7):1118-1135.e5