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

Elucidating the function of class 4 semaphorins in GABAergic synapse formation  

Synapses are specialized sites of cell-cell contact that mediate communication between neurons in the nervous system. Much remains to be discovered about the molecular mechanisms that underlie formation of these critical structures in the mammalian central nervous system. While recent advances have contributed to understanding of excitatory synapse formation, the processes that mediate inhibitory synapse formation remain poorly defined. In addition, it is hypothesized that aberrant synapse formation and function contributes to neurological disorders such as mental retardation, autism spectrum disorders, and epilepsy. To appreciate how synapse dysfunction contributes to these widespread neurological impairments, it is important to first understand how synapses are formed, maintained, and function in the non-pathological state. To this end, a novel, forward genetic RNA interference (RNAi)-based screen in cultured hippocampal neurons was developed that has identified new molecules required for synapse formation. Using this technique, it was discovered that RNAi-mediated knockdown of a class 4 Semaphorin, Sema4D, led to a decrease in the density of inhibitory synapses without an apparent effect on excitatory synapse formation. Thus, Sema4D is one of only a few molecules identified thus far that preferentially regulates inhibitory synapse formation. Therefore, this project to understand the mechanism of action of Sema4D in this process may yield key insights into the assembly of inhibitory synapses in the mammalian central nervous system. Project Status


Funder National Institutes of Health
Fiscal Year Funding $320,250.00
Current Award Period 2010-2015
Project Number 1R01NS065856-01A2
Principal Investigator Paradis, Suzanne
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? Federal
Institution Brandeis University
State/Country Massachusetts
Web Link 1 Elucidating the function of class 4 semaphorins in GABAergic synapse formation (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects N/A