Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

作     者：Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You Baicheng Zhao;Hang Zhang;Ying Liu;Gaoyu Zu;Yuxiao Zhang;Jiayi Hu;Shuai Liu;Linya You

作者机构：Department of Human Anatomy&HistoembryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina Shanghai Key Laboratory of Brain Functional Genomics(Ministry of Education)Affiliated Mental Health Center(ECNU)School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina Shanghai Changning Mental Health CenterShanghaiChina NYU-ECNU Institute of Brain and Cognitive Science at NYU ShanghaiShanghaiChina Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of ShanghaiShanghaiChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2024年第19卷第5期

页      面：1133-1141页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,No. 81771228 Shanghai Association of Science and Technology,Nos. 22WZ2501700 and 23WZ2504500 (all to LY) 

主　　题：behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current mRNA-Seq 

摘      要：Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/***1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual *** previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and ***,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory *** test this,we knocked out Brpf1 in forebrain excitatory neurons using *** found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in *** findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.