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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

The role of intracellular metabotropic glutamate receptor 5 at the synapse

Principal Investigator

Principal Investigator

Hogan, Carolyn

Description

Description

This is an individual National Research Service Award for pre-doctoral training for an M.D./Ph.D. student. By coupling to various intracellular cascades, metabotropic glutamate receptor 5 (mGluR5) plays an important role throughout the central nervous system (CNS) in modulating neuronal activity and synaptic transmission. Dysfunction of mGluR5 is implicated in a variety of neurological problems including anxiety, seizures, addiction, learning and memory disorders, and fragile X syndrome (FXS). In FXS, a single-gene disorder characterized by mental retardation and a range of autistic features, an expanded trinucleotide repeat results in a deficiency of fragile X mental retardation protein (FMRP). FMRP normally acts as a translational repressor to oppose mGluR5 signaling; thus, the lack of FMRP in FXS leads to overactivity of mGluR5. Although G-protein coupled receptors like mGluR5 are traditionally thought to initiate their signaling cascades from the cell surface, there is mounting evidence that intracellular receptors are also physiologically significant. This project will test the hypothesis that activation of intracellular mGluR5 versus cell surface mGluR5 has differential effects on protein synthesis and AMPA receptor (an excitatory ionotropic glutamate receptor) internalization in the hippocampus, an area important in learning and memory. Using sets of permeable and impermeable mGluR5 agonists and antagonists, activation of intracellular mGluR5 or cell surface mGluR5 can be achieved in isolation in order to delineate their downstream effects. For fragile X syndrome and possibly autism, understanding the role of intracellular mGluR5 will be crucial in developing suitable mGluR5 antagonists for therapeutic treatments.

Funder

Funder

National Institutes of Health

Fiscal Year Funding

Fiscal Year Funding

25890

Current Award Period

Current Award Period

2010-2013

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

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.

Project Link

Project Link

The role of intracellular metabotropic glutamate receptor 5 at the synapse (External web link)

Institution

Institution

Washington University in St. Louis

State/Country

State/Country

Missouri

Project Number

Project Number

1F30MH091998-01

Federal or Private?

Federal or Private?

Federal

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

N/A

 
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