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Regulation of habenular G-protein gamma 8 on learning and memory via modulation of the central acetylcholine system

Title
Regulation of habenular G-protein gamma 8 on learning and memory via modulation of the central acetylcholine system
Authors
Lee, Hyun-juChoi, Tae-IkKim, Yong-MinLee, SoonjeHan, BingBak, In SeonMoon, Sun AeYu, Dae-YeulShin, Ki SoonKim Kwon, YunheeMoon, CheilRyu, Jae HwanHoe, Hyang-SookKim, Cheol-HeeShim, Insop
DGIST Authors
Lee, Hyun-ju; Choi, Tae-Ik; Kim, Yong-Min; Lee, Soonje; Han, Bing; Bak, In Seon; Moon, Sun Ae; Yu, Dae-Yeul; Shin, Ki Soon; Kim Kwon, Yunhee; Moon, Cheil; Ryu, Jae Hwan; Hoe, Hyang-Sook; Kim, Cheol-Hee; Shim, Insop
Issue Date
ACCEPT
Citation
Molecular Psychiatry
Type
Article
Article Type
Article in press
Keywords
INTERPEDUNCULAR NUCLEUSSYNAPTIC PLASTICITYNICOTINE WITHDRAWALFEAR MEMORYRECEPTORSRATANXIETYSUBUNITNEURONSCOLOCALIZATION
ISSN
1359-4184
Abstract
Guanine nucleotide binding protein (G protein) gamma 8 (Gng8) is a subunit of G proteins and expressed in the medial habenula (MHb) and interpeduncular nucleus (IPN). Recent studies have demonstrated that Gng8 is involved in brain development; however, the roles of Gng8 on cognitive function have not yet been addressed. In the present study, we investigated the expression of Gng8 in the brain and found that Gng8 was predominantly expressed in the MHb–IPN circuit of the mouse brain. We generated Gng8 knockout (KO) mice by CRISPR/Cas9 system in order to assess the role of Gng8 on cognitive function. Gng8 KO mice exhibited deficiency in learning and memory in passive avoidance and Morris water maze tests. In addition, Gng8 KO mice significantly reduced long-term potentiation (LTP) in the hippocampus compared to that of wild-type (WT) mice. Furthermore, we observed that levels of acetylcholine (ACh) and choline acetyltransferase (ChAT) in the MHb and IPN of Gng8 KO mice were significantly decreased, compared to WT mice. The administration of nAChR α4β2 agonist A85380 rescued memory impairment in the Gng8 KO mice, suggesting that Gng8 regulates cognitive function via modulation of cholinergic activity. Taken together, Gng8 is a potential therapeutic target for memory-related diseases and/or neurodevelopmental diseases. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
URI
http://hdl.handle.net/20.500.11750/12434
DOI
10.1038/s41380-020-00893-2
Publisher
Nature Publishing Group
Related Researcher
  • Author Moon, Cheil Laboratory of Chemical Senses
  • Research Interests Brain convergent science based on chemical senses; olfaction; 감각신경계 기반 뇌융합과학; 후각 신경계
Files:
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Collection:
Department of Brain and Cognitive SciencesLaboratory of Chemical Senses1. Journal Articles


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