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 

机构地区：[1]Department of Human Anatomy&Histoembryology,School of Basic Medical Sciences,Fudan University,Shanghai,China [2]Shanghai Key Laboratory of Brain Functional Genomics(Ministry of Education),Affiliated Mental Health Center(ECNU),School of Psychology and Cognitive Science,East China Normal University,Shanghai,China [3]Shanghai Changning Mental Health Center,Shanghai,China [4]NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai,Shanghai,China [5]Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai,Shanghai,China

出　　处：《Neural Regeneration Research》2024年第5期1133-1141,共9页中国神经再生研究（英文版）

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)

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/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our 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 memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We 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 mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

关 键 词：behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current MRNA-SEQ 

分 类 号：R741[医药卫生—神经病学与精神病学]