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Molecular Cell & Developmental Biology
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The mammalian brain contains billions of neurons that make even more billions of synaptic connections. These connections allow us to perceive the outside world, and are the framework for higher cognitive functions such as learning, memory, thought and emotion. My lab is interested in understanding how neural connections are generated during development. It is thought that there is a combination of molecular cues and neural-activity dependant cues that help guide axons to their proper location and strengthen appropriate synapses. One family of molecular cues that are important for the development of CNS connections is the Eph family of receptor tyrosine kinases and their ligands, the ephrins. Our lab studies the role of these genes in the development of the visual system in the mouse. We use a combination of expression analysis, in vitro assays, electrophysiological and gene-knock out experiments to elucidate molecular mechanisms of CNS connectivity. For example, we have found that a class of axon guidance molecules called ephrins, combined with neural activity dependant processes are all that is required to make a topographic map. We are currently trying to understand both the mechanisms by which ephrins and neural activity act together to direct axon guidance in the visual system.
Cory Pfeiffenberger, Jena Yamada, and David A. Feldheim. Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system. J. Neurosci. In press Cang J, Kaneko M, Yamada J, Woods G, Stryker MP, Feldheim, DA. Ephrin-As Guide the Formation of Functional Maps in the Visual Cortex. Neuron, 2005 2005 Nov23 48(4) 577-89. Pfeiffenberger C, Cutforth T, Woods G, Yamada J, Renteria RC, Copenhagen DR,
Flanagan JG, Feldheim DA. Ephrin-As and neural activity are required for
eye-specific patterning during retinogeniculate mapping. Nat Neurosci. 2005
Aug;8(8):1022-7 Kramer S, Xie H, Gaff J, Williamson JR, Tkachenko AG, Nouri N, Feldheim DA, Feldheim DL. Preparation of Protein Gradients through the Controlled Deposition of Protein-Nanoparticle Conjugates onto Functionalized Surfaces. Journal of the American Chemical Society 126(17):5388-5395, 2004.
Feldheim, D.A., Kim, Y.I., Bergemann, A.D., Frisen, J., Barbacid, M. and Flanagan, J.G .Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping. Neuron 25: 563-74 (2000).
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