Department of
Psychological and Brain Sciences

• Development of neural circuitry, particularly in the neocortex
• Activity-dependent remodeling and mis-wiring in autism, dyslexia, schizophrenia, and congenital epilepsy
• Neuroprotective strategies

Mis-wiring of neuronal circuits during early life is likely to be a major cause of neurological disorders, including autism and schizophrenia. The Lu lab is intersted in how activity-dependent processes during brain development fine-tune the establishment of neural circuits and how sensory experiences affect neural circuit wiring and cognitive behaviors. Specifically, we are interested in exploring the role of the metabotropic glutamate receptor 5 (mGluR5), a group 1 metabotropic glutamate receptor. mGluR5 mutations have been identified in some ADHD and schizophrenic patients. We employ mouse genetic tools to understand the contribution of mGluR5 signaling in specific neuronal populations to sensory circuit formation, synaptic function/plasticity, and behavior. We are also exploring the role of the endogenous cannabinoid (endocannabinoid) system in fetal brain development and investigating how prenatal cannabis exposure affects brain development and later behaviors. Understanding the effects of endocannabinoids during neural circuit formation will not only shed light on normal brain development and function but will also allow us to assess endocannabinoid-based therapies and the effects of cannabis use on the developing fetus.

Proper brain function requires an active maintenance program to sustain neuronal health. Environmental stressors detrimentally impact the nervous system, predisposing it to neuronal dysfunction and degeneration if neuroprotective mechanisms are weakened. Recent studies by others and us revealed that NMNAT2 (nicotinamide mononucleotide adenylyl transferase 2) is a neuroprotective protein that is central to maintain neuronal integrity and facilitate proper neural function throughout life. NMNAT2 abundance is significantly reduced in Alzheimer’s Disease (AD) brains. Increasing  Nmnat2 expression in neurodegenerative animal models reduced neurodegeneration.  We hope to elucidate the mechanisms underlying NMNAT2’s neuroprotection and how NMNAT2 expression is down-regulated in pathological conditions.  In addition, we hope to develop NMNAT2-specific therapies to prevent or reduce neurodegeneration.

• Baiping Wang, Zilai Wang, Lu Sun, Li Yang, Hongmei li, Allysa Cole, Jennifer Rodriguez-Rivera, Hui-Chen Lu, Hui Zheng (2014) “The Amyloid Precursor Protein Controls Adult Hippocampal Neurogenesis through GABAergic Interneurons”, in press for Journal of Neuroscience.
• Tabassum Majid, Yousuf O. Ali, Deepa V. Venkitararamani, Ming-Kuei Jang, Hui-Chen Lu, Robia G Pautler (2014) “In vivo axonal transport deficits in a mouse model of fronto-temporal dementia”, Neuroimage: Clinical, 4:711-7.
• Chia-Shan Wu, Daniel Morgan, Chris P. Jew, Chris Haskins, Mary-Jeanette Andrews, Corinne M. Spencer, Traci Czyzyk, Heather Bradshaw, Ken Mackie, Hui-Chen Lu (2014) “Long-term consequences of perinatal fatty acid amino hydrolase inhibition”, British J. Pharmacology, 171:1420-34.
• Yousuf O. Ali, David Li-Kroeger, Hugo Bellen, R. Grace Zhai, Hui-Chen Lu (2013) NMNATs, evolutionary conserved neuronal maintenance factors, Trends in Neuroscience, 36:632-40.
• YanGang Sun, Juan Pita-Almenar, Chia-Shan Wu, John J Renger, Victor N. Uebele, Hui-Chen Lu, Michael Beierlein (2013) Biphasic cholinergic synaptic transmission controls action potential activity in thalamic reticular nucleus neurons, Journal of Neuroscience 33: 2048-59.
• Chia-Shan Wu, Hongmei Chen, Hao Sun, Jie Zhu, Chris P. Jew, Jim Wager-Miller, Alex Straiker, Corinne Spencer, Heather Bradshaw, Ken Mackie, Hui-Chen Lu (2013) GPR55, a G protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination, PLoS One. 8:e60314.
• Chris P. Jew, Chia-Shan Wu, Hao Sun, Jie Zhu, Jui-Yen Huang, Dinghui Yu, Nicholas J. Justice, Hui-Chen Lu (2013) mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion, PLoS One, 8:e70415.
• Kihoon Han,J. Lloyd Holder Jr, Christian P. Schaaf, Hui Lu,  Hongmei Chen, Hyojin Kang, Jianrong Tang, Zhenyu Wu, Shuang Hao, Sau Wai Cheung, Peng Yu, Hao Sun, Amy M. Breman, Ankita Patel, Hui-Chen Lu, Huda Y. Zoghbi (2013) SHANK3 duplication causes a hyperkinetic neuropsychiatric disorder with unique pharmacogenetic properties, Nature 503:72–7.
• Cecilia Ljungberg, Yousuf Ali, Jie Zhu, Chia-Shan Wu, Kazuhiro Oka, R.Grace Zhai, Hui-Chen Lu (2012) CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy, Human Mol. Genetics, 15:251-67.
• Javier Díaz, Tania Aguado, Chia-Shan Wu, Javier Palazuelos, Beat Lutz, Hui-Chen Lu, Manuel Guzmán, Ismael Galve-Roperh (2012) CB1 cannabinoid receptor regulation of Pax-6 and Tbr-2 controls pyramidal neurogenesis and cortical layer specification, Journal of Neuroscience 32: 16651-65.
• Chia-Shan Wu, Christopher P. Jew, Hui-Chen Lu (2011) Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain, Future Neurology, 6:459-480.
• Chia-Shan Wu, Carlos J Ballester Rosado, Hui-Chen Lu (2011) What can we learn from BARRELs? - The rodent barrel cortex as a model to study the establishment of neural circuits, European J. Neuroscience, 34:1663-76.
• YanGang Sun, Chia-Shan Wu, Hui-Chen Lu, Michael Beierlein (2011) Target-dependent control of synaptic inhibition by endocannabinoids in the thalamus, Journal of Neuroscience, 31:9222-30.
• Carlos J Ballester Rosado, Michael J Albright, Chia-Shan Wu, Chun-Chieh Liao, Jie Zhu, Shen-Ju Chou, Dennis D O'Leary, Li-Jen Lee, and Hui-Chen Lu (2010) mGluR5 in cortical excitatory neurons exerts both cell autonomous and nonautonomous influences on cortical somatosensory circuit formation, Journal of Neuroscience, 30:16896-909.
• Hsiao-Tuan Chao, Hongmei Chen, Rodney C. Samaco, Mingshan Xue, Maria Chahrour, Jong Yoo, Jeffrey L. Neul, Shiaoching Gong, Hui-Chen Lu, Nathaniel Heintz, Marc Ekker, John L.R. Rubnenstein, Jeffrey L, Noebels, Christian Rosenmund, Huda Y. Zoghbi (2010) GABAergic dysfunction mediates autism-like stereotypies and numerous features of Rett syndrome, Nature, 468(7321):263-9.
• Chia-Shan Wu, Jie Zhu, Jim Wager-Miller, Shan Wang, Dennis O'Leary, Krisztina Monory, Beat Lutz, Ken Mackie, and Hui-Chen Lu (2010) Requirement of cannabinoid CB1 receptor in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections, European J. Neuroscience, 32:693-706.
• Wei-Chi She, Charles Quairiaux, Michael J. Albright, Yu-Chi Wang, Denisse E. Sanchez, Poh-Shing Chang, Egbert Welker, Hui-Chen Lu (2009) Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway, European J. Neuroscience, 29: 1379–96 (EJN featured article).
• Jane E. Lauckner, Jill B. Jensen, Huei-Ying Chen, Hui-Chen Lu, Bertil Hille, and Ken Mackie (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current, Proc Natl Acad Sci U S A, 105: 2699-04.
• Jan Mulder, Tania Aguado, Erik Keimpema, Klaudia Barabás, Carlos J. Ballester Rosado, Laurent Nguyen, Krisztina Monory, Giovanni Marsicano, Vincenzo Di Marzo, Yasmin L. Hurd, Francois Guillemo, Ken Mackie, Beat Lutz, Manuel Guzman, Hui-Chen Lu, Ismael Galve-Roperh, Tibor Harkany (2008) Endocannabinoid signaling controls pyramidal cell specification and corticothalamic axon patterning, Proc Natl Acad Sci U S A, 105:8760-765.
• Hui-Chen Lu, Daniel A Butts, Pascal S. Kaeser, Wei-Chi She, Roger Janz and Michael C. Crair (2006) Role of efficient neurotransmitter release in barrel map development, Journal of Neuroscience, 26: 2692-703.
• James Carson, Tao Ju, Hui-Chen Lu, Christina Thaller, Mei Xu, Sarah L. Pallas, Joe Warren, Michael C. Crair, Wah Chiu, and Gregor Eichele (2005) A digital atlas to characterize the mouse brain transcriptome, PLoS Comput Bio,1: e41.
• Hui-Chen Lu, Wei-Chi She, Daniel T. Plas, Paul E. Neumann, Roger Janz, Michael C. Crair (2003) PKA mediated AMPARs trafficking in mouse cortical ‘barrel’ map development, Nature Neuroscience, 6: 939-47.
• Hui-Chen Lu, Ernesto Gonazlez, and Michael C. Crair (2001) Barrel cortex critical period plasticity is independent of changes in NMDA receptor subunit composition, Neuron, 32: 619-34.