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. Specifically, during the 2015 fiscal year, we have made following progress:
For research Aim 1 : we have successfully determined the role of GSG1L, a tetraspanning protein that binds to AMPARs in the regulation of excitatory synaptic strength and animal behavior with a combination of electrophysiological, molecular and cellular biological, genetic and behavioral approaches. We found that GSG1L plays a unique and critical role in the negative regulation of AMPAR-mediated synaptic transmission. In addition, GSG1L plays a distinct role in the modulation of AMPAR gating. Currently a manuscript for this work is under revision.
For research Aim 2 : we have revealed several key molecular processes that are critical for the development of inhibitory synapses. We found that activities of glutamate receptors in developing neurons are crucial for inhibitory synapse development. Current a revised manuscript for this work has been submitted.
For research Aim 3, we have identified two novel proteins that interact with NMDA receptors. Currently we are working to determine the function of these interactions in the regulation of excitatory synaptic transmission and synaptic plasticity.
For research Aim 4, we have made significant progress to determine the role of glutamatergic input onto midbrain dopamine neurons. During the 2015 fiscal year, we have performed series of behavioral experiments in the mutant mice in which the majority of glutamatergic input onto midbrain dopamine neurons has been genetically inactivated. These experiments demonstrate that glutamatergic input onto dopamine neurons plays a specific and prominent role in behavioral processes that require high-level motivation. Currently, a manuscript about this work is in preparation. Finally, during the 2015 fiscal year, we have collaborated with Dr. Katherine Roche group at NINDS, NIH to study the function of synaptic proteins, which resulted in one publication. In addition, we collaborated with Dr. Veronica Alvarezas lab at NIAAA to measure dopamine in the mutant mice lacking glutamatergic input onto dopamine neurons.

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4
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2015
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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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