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

Hyun ju Lee, Tae Ik Choi, Yong Min Kim, Soonje Lee, Bing Han, In Seon Bak, Sun Ae Moon, Dae Yeul Yu, Ki Soon Shin, Yunhee Kim Kwon, Cheil Moon, Jae Hwan Ryu, Hyang Sook Hoe, Cheol Hee Kim, Insop Shim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3737-3750
Number of pages14
JournalMolecular Psychiatry
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2021

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