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

A systematic test of the relation of ASD heterogeneity to synaptic function  

Although autism spectrum disorders (ASDs) are highly heritable, ASDs are heterogeneous, and no single genetic cause contributes to ASDs in a large proportion of patients. Instead, heterogeneous genetic changes, including many single gene mutations and copy-number variations (CNVs) are found in ASDs. Thus, a key question is whether different genetic changes contribute to ASDs via multiple, independent, pathogenic pathways, or whether the various genetic changes in ASDs converge onto a single pathogenic pathway. Several independent mutations in genes encoding synaptic proteins suggest that ASDs may generally involve an impairment of synaptic communication between neurons. Thus, the major goal of this project is to conduct a large scale, systematic analysis of the changes in neuron-to-neuron communication caused by the genes associated with autism. The approach will be to over express (to mimic gene duplications) or knock down (to mimic gene inactivations) mRNAs corresponding to 81 ASD candidate genes and to test the effect of these manipulations on synapses using standardized assays. Cell viability, neuronal development, synapse density, and synapse function will be assessed in cultured mouse neurons using optical and electro-physiological assays. The results of this project will provide a standardized reference point for the function of ASD candidate genes and provide an initial test of the hypothesis that despite their clinical and genetic heterogenity, ASDs involve a common, if diverse, pathway acting on synaptic communication in the brain. Project Status


Funder National Institutes of Health
Fiscal Year Funding $898,037.00
Project Number 1R01MH089054-01
Principal Investigator Sudhof, Thomas
Received ARRA Funding? Yes
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Strategic Plan Objective New! Green dot: Objective has greater than or equal to the recommended funding. 2SG. Support five studies that associate specific genotypes with functional or structural phenotypes, including behavioral and medical phenotypes (e.g., nonverbal individuals with ASD and those with cognitive impairments) by 2015. IACC Recommended Budget: $22,600,000 over 5 years.
Federal or Private? Federal
Institution Stanford University
State/Country California
Web Link 1 A systematic test of the relation of ASD heterogeneity to synaptic function (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects A systematic test of the relation of ASD heterogeneity to synaptic function | $875,864.00 | 2010 | 5R01MH089054-02