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
Lutz B*, Lu HC*, Eichele G, Miller D, Kaufman TC (1996) Rescue of Drosophila labial null mutant by
the chicken ortholog Hoxb-1 demonstrates that the function of Hox genes is phylogenetically conserved.
Genes and Development 10:176-184. (*Equal contribution)
Lu HC, Eichele G, Thaller C (1997) Ligand-bound RXR can mediate retinoid signal transduction during
embryogenesis. Development 124:195-203.
Lu HC, Revelli JP, Goering L, Thaller C, Eichele G (1997) Retinoid signaling is required for the establishment of a
ZPA and for the expression of Hoxb-8, a mediator of ZPA formation. Development 124:1643-1651.
Lu HC, Swindell EC, Sierralta WD, Eichele G, Thaller C (2001) Evidence for a role of protein kinase C in FGF signal
transduction in the developing chick limb bud. Development 128:2451-2460.
Lu HC, Gonzalez E, Crair MC (2001) Barrel cortex critical period plasticity is independent of changes in NMDA
receptor subunit composition. Neuron 32:619-634.
Lu HC, She WC, Plas DT, Neumann PE, Janz R, Crair MC (2003) Adenylyl cyclase I regulates AMPA receptor
trafficking during mouse cortical ‘barrel’ map development. Nature Neuroscience 6:939-947.
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)
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.
Contact Information
- Hui-Chen Lu Ph.D.
- The Cain Foundation Laboratories
- The Feigin Center, Suite 955 MC 3-6365
- 1102 Bates Street
- Houston, Texas 77030, U.S.A.
- Website
- Tel: (832) 824-3966
- Fax: (832) 825-4217
- E-mail: hclu@bcm.edu
|
