Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit.

Autor:	Kim DI; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Park S; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA., Park S; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Ye M; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Chen JY; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA., Kang SJ; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Jhang J; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Hunker AC; Department of Pharmacology, University of Washington, Seattle, WA 98195, USA., Zweifel LS; Department of Pharmacology, University of Washington, Seattle, WA 98195, USA., Caron KM; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Vaughan JM; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Saghatelian A; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Palmiter RD; Howard Hughes Medical Institute, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA., Han S; Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon 16419, Republic of Korea; Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: sunghan@salk.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Sep 05; Vol. 187 (18), pp. 5102-5117.e16. Date of Electronic Publication: 2024 Jul 22.
DOI:	10.1016/j.cell.2024.06.035
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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