VGLUT3 neurons in median raphe control the efficacy of spatial memory retrieval via ETV4 regulation of VGLUT3 transcription  

作　　者：Aodi He Chen Zhang Xiao Ke Yao Yi Quntao Yu Tongmei Zhang Hongyan Yu Huiyun Du Hao Li Qing Tian Ling-Qiang Zhu Youming Lu 

机构地区：[1]Department of Physiology,School of Basic Medicine and Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Wuhan Center for Brain Science,Huazhong University of Science and Technology,Wuhan 430030,China [3]Department of Pathophysiology,School of Basic Medicine,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Science China(Life Sciences)》2022年第8期1590-1607,共18页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (31721002, 81920208014, 31930051, 81800133);China Postdoctoral Science Foundation Funded Project (2018M642853)。

摘　　要：The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons(PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease(AD mice),VGLUT3→PGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3→PGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.

关 键 词：VGLUT3 median raphe nucleus parvalbumin-expressing GABA interneurons spatial memory retrieval ETV4 Alzheimer's disease 

分 类 号：R338[医药卫生—人体生理学]