김동일 (Salk Institute for Biological Studies)

한빛사논문

조회372

Salk Institute for Biological Studies

Cell, July 22, 2024 | https://doi.org/10.1016/j.cell.2024.06.035 Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit

Dong-Il Kim,¹ Sekun Park,² Seahyung Park,¹ Mao Ye,¹ Jane Y. Chen,² Sukjae J. Kang,¹ Jinho Jhang,¹Avery 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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-23)
연구진국내(교신)+국외 연구진
분야 생명과학 > 신경생물학

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