美国索尔克生物研究所Sung Han小组发现，肽能传导的突触前传感器和沉默器揭示神经肽是桥脑恐惧回路中的主要传导物质。相关论文于2024年7月22日在线发表于国际学术期刊《细胞》。
研究人员开发了两种用于研究行为小鼠中肽能传递的遗传编码工具：一种检测突触前神经肽释放的大型致密核心囊泡（LDCV）传感器和一种专门在LDCV内降解神经肽的遗传编码抑制器。利用这些工具，研究人员展示了在巴普洛夫威胁学习过程中，旁臂核到杏仁核的威胁路径中是神经肽而不是谷氨酸编码无条件刺激。
研究人员还展示了在杏仁核到旁臂核的内源性阿片样肽回路中，神经肽在编码正向情感和抑制条件性威胁反应中起重要作用。这些结果表明，这些突触前肽能传递传感器和抑制器是研究清醒、行为活跃动物中肽能系统的可靠工具。
据悉，神经元通过产生和释放神经肽来相互交流。尽管神经肽在大脑功能中具有重要性，但基于神经回路的肽能传递机制仍然不清楚，主要是由于缺乏在体内监测和操控神经肽释放的工具。
附：英文原文
Title: Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit
Author: Dong-Il Kim, Sekun Park, Seahyung Park, Mao Ye, Jane Y. Chen, Sukjae J. Kang, Jinho Jhang, Avery C. Hunker, Larry S. Zweifel, Kathleen M. Caron, Joan M. Vaughan, Alan Saghatelian, Richard D. Palmiter, Sung Han
Issue&Volume: 2024-07-22
Abstract: Neurons produce and release neuropeptides to communicate with one another. Despitetheir importance in brain function, circuit-based mechanisms of peptidergic transmissionare poorly understood, primarily due to the lack of tools for monitoring and manipulatingneuropeptide release in vivo. Here, we report the development of two genetically encoded tools for investigatingpeptidergic transmission in behaving mice: a genetically encoded large dense corevesicle (LDCV) sensor that detects presynaptic neuropeptide release and a geneticallyencoded silencer that specifically degrades neuropeptides inside LDCVs. Using thesetools, we show that neuropeptides, not glutamate, encode the unconditioned stimulusin the parabrachial-to-amygdalar threat pathway during Pavlovian threat learning.We also show that neuropeptides play important roles in encoding positive valenceand suppressing conditioned threat response in the amygdala-to-parabrachial endogenousopioidergic circuit. These results show that our sensor and silencer for presynapticpeptidergic transmission are reliable tools to investigate neuropeptidergic systemsin awake, behaving animals.
DOI: 10.1016/j.cell.2024.06.035
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00709-8