机构:[1]Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China[2]College of Life Sciences, Peking University, Beijing 100871, China[3]Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China内科科室精神科昆明医科大学附属第一医院[4]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing 100069, China
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.
基金:
National Basic Research Project Grant (973 Program) from the Ministry of Science and Technology of China [2013cb835100]; National Science Foundation of ChinaNational Natural 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
第一作者机构:[1]Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
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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.2016,113(27):7644-7649.doi:10.1073/pnas.1602152113.
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,113,(27)
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 113..27(2016):7644-7649