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

Role of UBE3A in neocortical plasticity and function  

The researchers propose that disruption of a protein degradation pathway could cause autism and the related Angelman syndrome by preventing the necessary remodeling of neurons during development. The cycle of construction and destruction ensures that valuable synapses are built and strengthened, while inappropriate connections are removed. Mutations in the Ube3a gene disrupt the ubiquitin pathway and have been linked to Angelman syndrome which, like autism, is accompanied by an excess of weak synapses in the brain. Ehlers and Philpot propose that abnormal expression of Ube3a could cause both autism and Angelman syndrome because the synapses are not properly remodeled during postnatal development. They plan to test this hypothesis by manipulating the expression of Ube3a in mice and then studying the development of the visual cortex as an example of postnatal learning and synapse remodeling. Using electrophysiology, they plan to measure the signaling strength of synapses after a learning experience to ascertain the role of the ubiquitin pathway in the modification of neurons. The researchers have preliminary data that suggest the synapses are not remodeled in the absence of Ube3a, preventing the formation of the strong synapses that would be needed for memory formation. They plan to continue these studies and perform more cognitive and behavioral assays to characterize the consequences of having weak synapses. Ehlers and Philpot also propose that modified learning practices may be able to compensate for low levels of Ube3a. Preliminary experiments have shown that limiting sensory inputs helps Ube3a-deficient mice regain synaptic plasticity. Project Status
ONGOING

2009

Funder Simons Foundation
Fiscal Year Funding $490,000.00
Project Number 94339
Principal Investigator Ehlers, Michael
Received ARRA Funding? No
Strategic Plan Question Question 4: Which Treatments And Interventions Will Help? (Interventions)
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.
Federal or Private? Private
Institution Duke University
State/Country North Carolina
Web Link 1 Role of UBE3A in neocortical plasticity and function (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Role of UBE3A in neocortical plasticity and function | $490,000.00 | 2010 | 94339
Role of UBE3A in neocortical plasticity and function | $367,500.00 | 2008 | Project number unavailable