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 brain cognition, and will identify synaptic and neural circuit malfunctions that are involved in many neurological and mental disorders, such as epilepsy, Alzheimer's disease, depression and autism. Specifically, during the 2019 fiscal year, we have made following progress:
For research Aim 1, we have identified a novel auxiliary subunit of GABA-A receptors. Currently a manuscript describing this work has been accepted for publication in Science (In press).
For research Aim 2 : we have made important progress in determining the molecular mechanisms underlying GABAergic synapse development. Currently two manuscripts have been published during the fiscal year of 2019 (one is in press). These studies reveal a critical role of GABA-A receptors in establishment of GABAergic, but not glutamatergic, synapses during development, and a key role of Slitrk3 C-terminus in constructing inhibitory connections. In addition, we have determined how trans-synaptic interactions regulate GABAergic synapse development. Currently a manuscript describing this work is under preparation and will be submitted in a few months. Furthermore, we have made progress in understanding NMDAR-mediated signaling for GABAergic synaptogenesis. Finally, during the 2019 fiscal year, we have collaborated with Dr. Katherine Roche group at NINDS, NIH to study the function of Neuroligin1-PSD95 interaction, which led a publication in PNAS, and have collaborated with Dr. Samarjit Bhattacharyya at IISER, India, to study metabotropic glutamate receptor trafficking, which led a manuscript that has been submitted for publication. In addition, we have collaborated with Dr. Chris McBain at NICHD, Dr. Ron Petralia at NIDCD, Dr. Ling-Gang Wu at NINDS, Dr. Chengyu Liu at NHLBI, and Dr. Joseph Lynch at University of Queensland to study a novel GABA-A receptor auxiliary subunit, which led to a publication in Science (In press). We have also collaborated with Dr. Yelin Chen at Chinese Academy of Sciences working on a review article on NMDA receptors, which led to a publication in Brain Science Advances.

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8
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2019
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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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