Nature Communications (Apr 2023)

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

DOI
https://doi.org/10.1038/s41467-023-38180-7
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 17

Abstract

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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.