Neural mechanism of acute stress regulation by trace aminergic signalling in the lateral habenula in male mice

Soo Hyun Yang, Esther Yang, Jaekwang Lee, Jin Yong Kim, Hyeijung Yoo, Hyung Sun Park, Jin Taek Jung, Dongmin Lee, Sungkun Chun, Yong Sang Jo, Gyeong Hee Pyeon, Jae Yong Park, Hyun Woo Lee, Hyun Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Stress management is necessary for vertebrate survival. Chronic stress drives depression by excitation of the lateral habenula (LHb), which silences dopaminergic neurons in the ventral tegmental area (VTA) via GABAergic neuronal projection from the rostromedial tegmental nucleus (RMTg). However, the effect of acute stress on this LHb-RMTg-VTA pathway is not clearly understood. Here, we used fluorescent in situ hybridisation and in vivo electrophysiology in mice to show that LHb aromatic l-amino acid decarboxylase-expressing neurons (D-neurons) are activated by acute stressors and suppress RMTg GABAergic neurons via trace aminergic signalling, thus activating VTA dopaminergic neurons. We show that the LHb regulates RMTg GABAergic neurons biphasically under acute stress. This study, carried out on male mice, has elucidated a molecular mechanism in the efferent LHb-RMTg-VTA pathway whereby trace aminergic signalling enables the brain to manage acute stress by preventing the hypoactivity of VTA dopaminergic neurons.

Original languageEnglish
Article number2435
JournalNature communications
Volume14
Issue number1
DOIs
Publication statusPublished - 2023 Dec

Bibliographical note

Funding Information:
We thank NeuroVIS for performing the in vivo measurements of dopamine release, and Ulsan National Institute of Science and Technology Optical Biomed Imaging Center (UOBC) for the three-dimensional analysis of the neural circuit. We thank Drs. Yongsang Cho (Gachon Liberal Arts College, Gachon University), Il Hwan Kim (University of Tennessee Health Science Center), Kihoon Han (College of Medicine, Korea University), Woong Sun (College of Medicine, Korea University) and Gi Hoon Son (College of Medicine, Korea University) for their critical reading and comments. This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (NRF-2017M3C7A1079692 and NRF-2020M3E5D9080794 to H.K.; NRF-2017R1D1A1B06032730 to H.W.L.; E0210201-01 to J.L.; NRF-2022M3E5E8017804 to Y.S.J.; and NRF‐2018M3C7A1024597 to D.L.).

Funding Information:
We thank NeuroVIS for performing the in vivo measurements of dopamine release, and Ulsan National Institute of Science and Technology Optical Biomed Imaging Center (UOBC) for the three-dimensional analysis of the neural circuit. We thank Drs. Yongsang Cho (Gachon Liberal Arts College, Gachon University), Il Hwan Kim (University of Tennessee Health Science Center), Kihoon Han (College of Medicine, Korea University), Woong Sun (College of Medicine, Korea University) and Gi Hoon Son (College of Medicine, Korea University) for their critical reading and comments. This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (NRF-2017M3C7A1079692 and NRF-2020M3E5D9080794 to H.K.; NRF-2017R1D1A1B06032730 to H.W.L.; E0210201-01 to J.L.; NRF-2022M3E5E8017804 to Y.S.J.; and NRF‐2018M3C7A1024597 to D.L.).

Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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