The lab is interested in understanding molecular and cellular mechanisms underlying synapse formation and synaptic plasticity, and in the long term elucidating synaptic mechanisms underlying neuronal circuit function in animal behavior. We believe that these studies will provide fundamental insights into neural underpinnings for learning and memory, and will identify synaptic and neural circuit malfunctions that are involved in many neurological and mental disorders, such as Alzheimer's disease, depression and autism disorders. During the 2013 fiscal year, we have added another dual whole cell patch-clamp system in the lab for electrophysiological analysis of neuronal activity. We have also established ultra fast drug application system in the lab to study ion channel kinetics and optimized in utero cDNA electroporation at E14 to manipulate neuronal gene expression. In addition, we established several rodent animal behavioral paradigms in the lab, which allow us to study hippocampus-dependent learning and memory. Installation of these equipment and methodologies in the lab allow us to efficiently pursue our scientific goals. On the research side, we have successfully determined the role of a novel protein in the regulation of excitatory synaptic strength with a combination of electrophysiological, molecular and cellular biological and genetic approaches. Currently we are studying biochemical mechanisms underlying its function. In addition, the second line of research in the lab has revealed some key molecular events underlying synapse formation. Currently we are actively pursuing this project to determine molecular pathways involved in this process. In addition, we are collaborating with Dr. Katherine Roches group at NINDS, NIH to study AMPA receptor trafficking. We are also collaborating with Dr. Francis McMahons group at NIMH, NIH to study neuronal activity in iPSC-derived neurons.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$1,048,916
Indirect Cost
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State
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Gu, Xinglong; Lu, Wei (2018) Genetic deletion of NMDA receptors suppresses GABAergic synaptic transmission in two distinct types of central neurons. Neurosci Lett 668:147-153
Yeh, Chia-Yu; Asrican, Brent; Moss, Jonathan et al. (2018) Mossy Cells Control Adult Neural Stem Cell Quiescence and Maintenance through a Dynamic Balance between Direct and Indirect Pathways. Neuron 99:493-510.e4
Steinkellner, Thomas; Zell, Vivien; Farino, Zachary J et al. (2018) Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons. J Clin Invest 128:774-788
Li, Jun; Han, Wenyan; Pelkey, Kenneth A et al. (2017) Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development. Neuron 96:808-826.e8
Liu, Shuxi; Zhou, Liang; Yuan, Hongjie et al. (2017) A Rare Variant Identified Within the GluN2B C-Terminus in a Patient with Autism Affects NMDA Receptor Surface Expression and Spine Density. J Neurosci 37:4093-4102
Lu, Wei; Bromley-Coolidge, Samantha; Li, Jun (2017) Regulation of GABAergic synapse development by postsynaptic membrane proteins. Brain Res Bull 129:30-42
Mao, Xia; Gu, Xinglong; Lu, Wei (2017) GSG1L regulates the strength of AMPA receptor-mediated synaptic transmission but not AMPA receptor kinetics in hippocampal dentate granule neurons. J Neurophysiol 117:28-35
Han, Wenyan; Wang, Huiqing; Li, Jun et al. (2017) Ferric Chelate Reductase 1 Like Protein (FRRS1L) Associates with Dynein Vesicles and Regulates Glutamatergic Synaptic Transmission. Front Mol Neurosci 10:402
Lu, Wei; Chen, Yelin (2017) Development of fast neurotransmitter synapses: General principle and recent progress. Brain Res Bull 129:1-2
Gu, Xinglong; Zhou, Liang; Lu, Wei (2016) An NMDA Receptor-Dependent Mechanism Underlies Inhibitory Synapse Development. Cell Rep 14:471-478

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