Inability to activate Rac1-dependent forgetting contributes to   behavioral inflexibility in mutants of multiple autism-risk genes

doi:10.1073/pnas.1602152113

CORC > 北京大学 > 生命科学学院

	Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes
	Dong, Tao ; He, Jing ; Wang, Shiqing ; Wang, Lianzhang ; Cheng, Yuqi ; Zhong, Yi
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2016
关键词	autism forgetting Rac1 behavioral flexibility Drosophila DE-NOVO MUTATIONS TUBEROUS SCLEROSIS COMPLEX LONG-TERM-MEMORY SPECTRUM DISORDERS ANGELMAN-SYNDROME DROSOPHILA-MELANOGASTER COGNITIVE FLEXIBILITY SYNAPTIC PLASTICITY UBIQUITIN LIGASE REGULATES SLEEP
DOI	10.1073/pnas.1602152113
英文摘要	The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes.; National Basic Research Project Grant (973 Program) from the Ministry of Science and Technology of China [2013cb835100]; National Science Foundation of China [91332207]; Tsinghua University Initiative Scientific Research Program [20111080956]; Yunnan Provincial Zhongyi Expert Workstation [2014IC046]; Tsinghua-Peking Joint Center for Life Sciences; SCI(E); PubMed; ARTICLE; zhongyi@tsinghua.edu.cn; 27; 7644-7649; 113
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/491947]
专题	生命科学学院
推荐引用方式 GB/T 7714	Dong, Tao,He, Jing,Wang, Shiqing,et al. Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2016.
APA	Dong, Tao,He, Jing,Wang, Shiqing,Wang, Lianzhang,Cheng, Yuqi,&Zhong, Yi.(2016).Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.
MLA	Dong, Tao,et al."Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016).