Glutamate receptors that are selective for N-methyl-D-aspartate (NMDA) are a major class of neurotransmitter receptors that are essential for brain function. Abnormal regulation and dysfunction of NMDA receptors have been associated with many brain disorders including epilepsy, autism, stroke, and schizophrenia. NMDA receptors play a critical role in the development of neuronal circuits, but the underlying mechanisms are poorly understood. In this proposal we focus on the role of NMDA receptors in the maturation of neurons and synapses during early life. Specifically, we will address two important questions: 1) What is the role of NMDA receptors in the development of function and morphology of neurons;and 2) What is the role of NMDA receptor alternative splicing in the maturation of excitatory synapses and in the regulation of network excitability. The answers to these questions have broad implications for brain disorders. We use a multidisciplinary approach to address these questions, taking advantage of genetic manipulation, electrophysiology, anatomy, and molecular analyses in the mouse.

Public Health Relevance

The proposed research will provide new insights into mechanisms of brain disorders including epilepsy, autism, stroke, and schizophrenia, and may lead to new strategies for the treatment of these diseases.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01NS064013-06A1
Application #
8813290
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Talley, Edmund M
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
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Wang, Hao; Liu, Hong; Zhang, Zhong-wei (2011) Elimination of redundant synaptic inputs in the absence of synaptic strengthening. J Neurosci 31:16675-84