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

Function and dysfunction of neuroligins in synaptic circuits  

Autism spectrum disorders (ASDs) contain a large genetic component, and many candidate genes that may cause ASDs have been identified. However, it remains unknown how mutations in these genes contribute to the development of ASDs. One approach to understanding a human disease is to replicate the pathological process in genetically modified mice. The present application is based on this approach, and focuses on proteins called neuroligins that perform central roles in synapses, which are junctions between nerve cells that allow these cells to communicate with each other. Strikingly, many mutations in neuroligin genes were identified in ASD patients, suggesting that analyzing neuroligins may provide insights into the critical pathways underlying the development of ASDs. The present application builds on preliminary studies in which we examined lines of mutant mice containing neuroligin mutations that were previously observed in human ASD patients. These studies showed that these mutant mice exhibit impaired behaviors, and that their synapses do not function normally. In particular, one mouse line carrying a single amino acid change in a specific neuroligin displayed striking decreases in social interactions, coupled to an increase in spatial learning, and to multiple changes in the communication between nerve cells at synapses. We now propose to study these and other mouse models of ASDs to elucidate how neuroligins normally regulate synapses, and how such regulation becomes abnormal when neuroligins are altered by mutations observed in ASD patients. Our studies will span multiple levels of analysis, ranging from examinations of purified proteins to investigations of mouse behavior and the properties of neural circuits in key brain regions. With this multidisciplinary approach, we will elucidate how neuroligins regulate synapses, and how such regulation becomes in impaired in ASDs, and hope to thereby provide critical advances for understanding the pathogenesis and for treatment of ASDs in general. Project Status


Funder Simons Foundation
Fiscal Year Funding $150,000.00
Current Award Period 2010-2013
Project Number 177850
Principal Investigator Sudhof, Thomas
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective 2O. Not specific to Question 2 objectives
Federal or Private? Private
Institution Stanford University
State/Country California
Web Link 1 Function and dysfunction of neuroligins in synaptic circuits (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects Function and dysfunction of neuroligins in synaptic circuits | $450,000.00 | 2011 | 177850
Function and dysfunction of neuroligins in synaptic circuits | $750,000.00 | 2012 | 177850