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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Talley, Edmund M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Jackson Laboratory
Bar Harbor
United States
Zip Code
Hou, Guoqiang; Zhang, Zhong-Wei (2017) NMDA Receptors Regulate the Development of Neuronal Intrinsic Excitability through Cell-Autonomous Mechanisms. Front Cell Neurosci 11:353
Zhang, Wen; Zhang, Lifeng; Liang, Bo et al. (2016) Hyperactive somatostatin interneurons contribute to excitotoxicity in neurodegenerative disorders. Nat Neurosci 19:557-559
Hou, Guoqiang; Smith, Alison G; Zhang, Zhong-Wei (2016) Lack of Intrinsic GABAergic Connections in the Thalamic Reticular Nucleus of the Mouse. J Neurosci 36:7246-52
Zhang, Wen; Peterson, Matthew; Beyer, Barbara et al. (2014) Loss of MeCP2 from forebrain excitatory neurons leads to cortical hyperexcitation and seizures. J Neurosci 34:2754-63
Zhang, Zhong-wei; Peterson, Matthew; Liu, Hong (2013) Essential role of postsynaptic NMDA receptors in developmental refinement of excitatory synapses. Proc Natl Acad Sci U S A 110:1095-100
Wang, Hao; Liu, Hong; Storm, Daniel R et al. (2011) Adenylate cyclase 1 promotes strengthening and experience-dependent plasticity of whisker relay synapses in the thalamus. J Physiol 589:5649-62
Wang, Hao; Liu, Hong; Zhang, Zhong-wei (2011) Elimination of redundant synaptic inputs in the absence of synaptic strengthening. J Neurosci 31:16675-84