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조회102

원상현Sanghyun Won

DGIST

Nat. Commun., 21 November 2024 | https://doi.org/10.1038/s41467-024-54376-x Astrocytic inhibition of lateral septal neurons promotes diverse stress responses

Kain Seo ^1,2,8, Sanghyun Won ^1,2,8, Hee-Yoon Lee ^3,8, Yeonju Sin¹, Sangho Lee ^1,2, Hyejin Park ⁴, Yong Geon Kim ¹, Seo Young Yang ¹, Dong-Jae Kim⁴, Kyoungho Suk ⁵, Ja Wook Koo ⁶, Myungin Baek ¹, Se-Young Choi ^3,*& Hyosang Lee^1,2,7,*

¹Department of Brain Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, Republic of Korea.
²Convergence Research Advanced Centre for Olfaction, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, Republic of Korea.
³Department of Physiology and Neuroscience, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Republic of Korea.
⁴Laboratory Animal Resource Center, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, Republic of Korea.
⁵Department of Pharmacology, School of Medicine, Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea.
⁶Emotion, Cognition and Behavior Research Group, Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.
⁷Korea Brain Research Institute (KBRI), Daegu, Republic of Korea.
⁸These authors contributed equally: Kain Seo, Sanghyun Won, Hee-Yoon Lee.

^*Corresponding authors: correspondence to Se-Young Choi or Hyosang Lee

Abstract

Inhibitory neuronal circuits within the lateral septum (LS) play a key role in regulating mood and stress responses. Even though glial cells can modulate these circuits, the impact of astrocytes on LS neural circuits and their functional interactions remains largely unexplored. Here, we demonstrate that astrocytes exhibit increased intracellular Ca²⁺ levels in response to aversive sensory and social stimuli in both male and female mice. This astrocytic Ca²⁺ elevation inhibits neighboring LS neurons by reducing excitatory synaptic transmissions through A1R-mediated signaling in both the dorsal (LSd) and intermediate LS (LSi) and enhancing inhibitory synaptic transmission via A2AR-mediated signaling in the LSi. At the same time, astrocytes reduce inhibitory tone on distant LS neurons. In the LSd, astrocytes promote social avoidance and anxiety, as well as increased heart rate in socially stressed male mice. In contrast, astrocytes in the LSi contribute to elevated heart rate and heightened blood corticosterone levels in unstressed male mice. These results suggest that the dynamic interactions between astrocytes and neurons within the LS modulate physiological and behavioral responses to stressful experiences.

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형식Research article
게재일2024년 11월 (BRIC 등록일 2024-12-23)
연구진국내 연구진
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