Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

MicroRNAs in synaptic plasticity and behaviors relevant to autism  

This is an NIH Independent Scientist Award, which is designed to foster the development of outstanding scientists and enable them to expand their potential to make significant contributions to their field of research. The primary goal of this research is to advance understanding of the molecular and cellular mechanisms underlying cognition and cognitive disorders. Recent evidence has implicated inappropriate or excessive synaptic protein synthesis in the pathogenesis of cognitive impairment and autism. The broad, long-term goals of this project are to understand the role of translational repression by microRNAs in synaptic plasticity, synaptic connectivity, and behaviors relevant to autism. MicroRNAs comprise a large family of endogenous 20-23 nucleotide noncoding RNAs that repress protein synthesis by binding to complementary sequences in target mRNAs. Intriguingly, the fragile X mental retardation protein (FMRP) interacts physically and genetically with the molecular machinery mediating translational repression by microRNAs. In addition, reduced microRNA expression has been associated with human autistic disorders. Based on these observations, microRNAs may regulate protein synthesis-dependent synaptic plasticity and memory, and loss of microRNA-mediated translational repression may lead to excessive synaptic protein synthesis, altered synaptic connectivity and autistic behavioral phenotypes. Conditional knockout mice in which microRNA expression is partially or completely inactivated in the postnatal forebrain will be analyzed in parallel with FMRP-deficient mice for behavioral deficits relevant to autism, impairments in protein synthesis-dependent synaptic plasticity and memory, and abnormalities in synaptic connectivity. Accomplishment of the proposed goals will increase understanding of the molecular and synaptic defects responsible for these cognitive disorders and possibly identify new therapeutic targets or strategies. Project Status


Funder National Institutes of Health
Fiscal Year Funding $131,220.00
Current Award Period 2010-2014
Project Number 1K02MH087796-01
Principal Investigator Kelleher, Raymond
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
Federal or Private? Federal
Institution Massachusetts General Hospital
State/Country Massachusetts
Web Link 1 MicroRNAs in synaptic plasticity and behaviors relevant to autism (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects N/A