Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 27, Pages 7644-7649Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1602152113
Keywords
autism; forgetting; Rac1; behavioral flexibility; Drosophila
Categories
Funding
- 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
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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.
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