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Assistant Professor, Baylor College of Medicine
B.S., National Taiwan University, Taiwan, 1991
Ph.D., Baylor College of Medicine, 1997
Postdoc, Baylor College of Medicine, 1997-2003
Molecular mechanisms of cortical map development
One prominent feature of the mammalian brain is the topographical representation of the external sensory world. Common examples are the homunculus map in somatosensory cortex representing the body surface and the retinotopic map in visual cortex. These maps are distinguished by their extraordinary precision, with organized arrays of afferents projecting into distinct neuronal modules. Remarkably, these cortical maps that form in every individual can be altered by exposure to abnormal sensory experience during a “critical period” of postnatal development. Mis-wiring of neuronal circuits during early life is likely to be a major cause for neurological disorders, including autism, dyslexia, schizophrenia, and congenital epilepsy.
What is the nature of such activity-dependent processes? How does sensory experience influence the organization of neural circuits? What determines the critical period of cortical map plasticity? We use mouse barrel map as a model system to explore the activity-dependent processes affecting cortical map development and plasticity to take advantage of the beautiful pattern as well as the power of transgenic mouse technology. The prominent anatomical feature of “barrels” has allowed the identification of several mutants with barrel map deficits, includes barrelless mice (the null mutant mice of calcium-activated adenylyl cyclase I, AC1), the loss-of-function mutant mice of mGluR5 (metabotropic glutamate receptor) and PKARIIβ (protein kinase A regulatory subunit II β subunit).
Our previous studies with barrelless mice strongly support the role of cAMP in activity-dependent processes in the precise whisker-to-barrel connections, and protein kinase A (PKA) is its major target. We will use several barrelless mice to focus on the role of cAMP/PKA signaling cascades in cortical map development. A combination of electrophysiological, pharmacological, anatomical, and biochemical techniques will be employed to elucidate the molecular mechanism underlying cortical map development and plasticity.
Selected Publications
Carson JP, Ju T, Lu HC, Thaller C, Xu M, Pallas SL, Crair MC, Warren J, Chiu W, Eichele G (2005) A digital atlas to characterize the mouse brain transcriptome. PLoS Computational Biology 1:e41. (http://www.geneatlas.org/gene/main.jsp)
Inan M, Lu HC, Albright MJ, She WC, Crair MC (2006) Barrel map development relies on protein kinase A regulatory subunit II beta-mediated cAMP signaling. Journal of Neuroscience 26:4338-4349.
Lu HC, Butts DA, Kaeser PS, She WC, Janz R, Crair MC (2006) Role of efficient neurotransmitter release in barrel map development. Journal of Neuroscience 26:2692-2703.
She WC, Quairiaux C, Albright MJ, Wang YC, Sanchez DE, Chang PS, Welker E, Lu HC (2009) Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway. European Journal of Neuroscience 29:1379-1396.
Wu CS, Zhu J, Wager-Miller J, Wang S, O’Leary D, Monory K, Lutz B, Mackie K, Lu HC (2010) Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections. European Journal of Neuroscience 32:693-706.
Ballester-Rosado CJ, Albright MJ, Wu CS, Liao CC, Zhu J, Xu J, Lee LJ, Lu HC (2010) mGluR5 in cortical excitatory neurons exerts both cell-autonomous and -nonautonomous influences on cortical somatosensory circuit formation. Journal of Neuroscience 30:16896-16909.
Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, Neul JL, Gong S, Lu HC, Heintz N, Ekker M, Rubenstein JL, Noebels JL, Rosenmund C, Zoghbi HY (2010) Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature 468:263-269.
Asprer JS, Lee B, Wu CS, Vadakkan T, Dickinson ME, Lu HC, Lee SK (2011) LMO4 functions as a co-activator of neurogenin 2 in the developing cortex. Development 138:2823-2832.
Ljungberg MC, Ali YO, Zhu J, Wu CS, Oka K, Zhai RG, Lu HC (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 Molecular Genetics 21:251-267.
Contact Information
Hui-Chen Lu Ph.D.
The Cain Foundation Laboratories
Baylor College of Medicine
1250 Moursund St. – NRI, Suite N1265.08
Houston, Texas 77030, U.S.A.
Tel: (832) 824-3966
Fax: (832) 825-1248
E-mail: