한빛사논문
Dong-Il Kim,1 Sekun Park,2 Seahyung Park,1 Mao Ye,1 Jane Y. Chen,2 Sukjae J. Kang,1 Jinho Jhang,1 Avery C. Hunker,3 Larry S. Zweifel,3 Kathleen M. Caron,4 Joan M. Vaughan,1 Alan Saghatelian,1 Richard D. Palmiter,2 and Sung Han 1,5,6,7,*
1Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
2Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
3Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
4Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
5Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon 16419, Republic of Korea
6Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
7Lead contact
*Corresponding author: correspondence to Sung Han
Abstract
Neurons produce and release neuropeptides to communicate with one another. Despite their importance in brain function, circuit-based mechanisms of peptidergic transmission are poorly understood, primarily due to the lack of tools for monitoring and manipulating neuropeptide release in vivo. Here, we report the development of two genetically encoded tools for investigating peptidergic transmission in behaving mice: a genetically encoded large dense core vesicle (LDCV) sensor that detects presynaptic neuropeptide release and a genetically encoded silencer that specifically degrades neuropeptides inside LDCVs. Using these tools, we show that neuropeptides, not glutamate, encode the unconditioned stimulus in the parabrachial-to-amygdalar threat pathway during Pavlovian threat learning. We also show that neuropeptides play important roles in encoding positive valence and suppressing conditioned threat response in the amygdala-to-parabrachial endogenous opioidergic circuit. These results show that our sensor and silencer for presynaptic peptidergic transmission are reliable tools to investigate neuropeptidergic systems in awake, behaving animals.
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