Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors

Seung Ha Kim; Jaegeon Lee; Mirae Jang; Seung-Eon Roh; Soobin Kim; Ji Hwan Lee; Jewoo Seo; Jinhee Baek; Jae Yoon Hwang; In Seon Baek; Yong-Seok Lee; Eiji Shigetomi; C Justin Lee; Schuichi Koizumi; Sun Kwang Kim; Sang Jeong Kim

doi:10.1038/s41593-024-01807-z

Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors

Nat Neurosci. 2025 Jan 2. doi: 10.1038/s41593-024-01807-z. Online ahead of print.

Authors

Seung Ha Kim^#^{1

2}, Jaegeon Lee^#^{1

2}, Mirae Jang^{1

2}, Seung-Eon Roh^{1

3

4}, Soobin Kim^{1

2}, Ji Hwan Lee³, Jewoo Seo^{1

2}, Jinhee Baek^{1

2}, Jae Yoon Hwang^{1

2}, In Seon Baek⁵, Yong-Seok Lee^{1

2

6}, Eiji Shigetomi^{7

8}, C Justin Lee⁹, Schuichi Koizumi^{7

8}, Sun Kwang Kim^{10

11}, Sang Jeong Kim^{12

13

14}

Affiliations

¹ Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
³ Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Korea.
⁴ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
⁶ Memory Network Medical Research Center, Neuroscience Research Institute, Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul, Korea.
⁷ Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.
⁸ Yamanashi GLIA Center, University of Yamanashi, Yamanashi, Japan.
⁹ Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Korea.
¹⁰ Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Korea. [email protected].
¹¹ Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Korea. [email protected].
¹² Department of Physiology, Seoul National University College of Medicine, Seoul, Korea. [email protected].
¹³ Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. [email protected].
¹⁴ Memory Network Medical Research Center, Neuroscience Research Institute, Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul, Korea. [email protected].

^# Contributed equally.

PMID: 39748107
DOI: 10.1038/s41593-024-01807-z

Abstract

The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC-NA signals by increasing intracellular calcium in an integrative manner ('flares'). BG flares were also elicited in response to an intraplantar capsaicin injection. Chemogenetic inactivation of LC terminals or BG in the cerebellar cortex or BG-specific knockdown of α₁-adrenergic receptors suppressed BG flares, reduced nocifensive licking and had analgesic effects in nerve injury-induced chronic neuropathic pain. Moreover, chemogenetic activation of BG or an intraplantar capsaicin injection reduced Purkinje cell firing, which may disinhibit the output activity of the deep cerebellar nuclei. These results suggest a role for BG in computing noxious information from the LC and in modulating pain-related behaviors by regulating cerebellar output.

Abstract

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