O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward
作者机构：Departments of Neurosurgery and Hand SurgeryHuashan HospitalState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceSchool of Basic Medical SciencesInstitutes of Brain ScienceFudan UniversityShanghai200032China
出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)
年 卷 期：2022年第38卷第3期
页 面：263-274页
核心收录：
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
基 金：the National Natural Science Foundation of China(31871021,82021002,31930046,and 32000671) the China Postdoctoral Science Foundation(2020M670978 and 2021T140127) the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01),and ZhangJiang Lab
主 题：O-GlcNAcylation Dopaminergic neurons Natural reward Motor learning
摘 要：Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways,and its disturbance has been found in neurodegenerative diseases and metabolic ***,its role in the mesolimbic dopamine(DA)system,especially in the ventral tegmental area(VTA),needs to be ***,we found that injection of Thiamet G,an O-GlcNAcase(OGA)inhibitor,in the VTA and nucleus accumbens(NAc)of mice,facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod *** with DAergic neuron-specific knockout of O-GlcNAc transferase(OGT)displayed severe metabolic abnormalities and died within 4–8 weeks after ***,mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose,and impaired motor learning in the rotarod ***,overexpression of OGT in GABAergic neurons in the VTA had no effect on these *** results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
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