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

doi:10.1016/j.neuron.2022.12.034

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

Neuron. 2023 Apr 5;111(7):1118-1135.e5. doi: 10.1016/j.neuron.2022.12.034. Epub 2023 Jan 26.

Authors

Jianzhi Zeng¹, Xuelin Li², Renzimo Zhang³, Mingyue Lv², Yipan Wang², Ke Tan⁴, Xiju Xia⁵, Jinxia Wan², Miao Jing⁶, Xiuning Zhang², Yu Li⁷, Yang Yang⁸, Liang Wang⁹, Jun Chu⁹, Yan Li⁸, Yulong Li¹⁰

Affiliations

¹ 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. Electronic address: zengjz@szbl.ac.cn.
² 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.
³ 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; 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; Yuanpei College, Peking University, Beijing 100871, China.
⁴ 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.
⁵ 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; PKU-THU-NIBS Joint Graduate Program, Beijing 100871, China.
⁶ Chinese Institute for Brain Research, Beijing 102206, China.
⁷ School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.
⁸ Institute of Biophysics, State Key Laboratory of Brain and Cognitive Science, Center for Excellence in Biomacromolecules, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁹ Guangdong Provincial Key Laboratory of Biomedical Optical Imaging Technology & Center for Biomedical Optics and Molecular Imaging & CAS Key Laboratory of Health Informatics, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
¹⁰ 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; Yuanpei College, Peking University, Beijing 100871, China; PKU-THU-NIBS Joint Graduate Program, Beijing 100871, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address: yulongli@pku.edu.cn.

PMID: 36706757
DOI: 10.1016/j.neuron.2022.12.034

Abstract

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.

Keywords: GRAB sensor; associative learning; coincidence time window; olfaction; serotonin; synaptic plasticity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Conditioning, Classical / physiology
Drosophila / physiology
Mushroom Bodies / physiology
Neurons / physiology
Serotonin*
Smell* / physiology

Substances

Serotonin

Abstract

Publication types

MeSH terms

Substances

Grants and funding