CAREER: Imaging Mechanisms of Dendritic Development in the Living Neuron

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Nerve cells (neurons) in the mammalian brain often have elaborate treelike branching of fine cellular extensions called dendritic arbors, which receive the chemical signals of activity from other neurons. Like an antenna, the location and number of branches on a dendritic arbor organize the pattern of the afferent input, so the decision about where and when to form a branch is critical. The intracellular structures of these dendrites include cytoskeletal components called actin and microtubules, and these components are dynamic, changing the dendritic structure over time by elongation or retraction or stabilization of the branches at particular points. It remains unclear what the mechanisms are that determine the patterning of these often highly specific arbors during development and growth. To approach this question, this project combines several recent technical advances that give the ability to 1) accelerate dendritic development significantly in cultured neurons from the hippocampal region of the brain; 2) follow the expression and trafficking of proteins and organelles within the living neuron by high-resolution microscopic time-lapse imaging; and 3) to create patterned substrates, using novel creative nanofabrication techniques to provide external cues for cellular development. The experiments will determine the roles of actin and microtubule dynamics, and the influence of external cues such as cell adhesion molecules and location of afferent contacts from other neurons, on dendritic branching. Results will provide a major advance on an important topic of neural development where fundamental information is still unknown, and the interdisciplinary approach will enhance interactions between biology and engineering. The excellent integration of educational activities with the research will have a major impact on research experience in this liberal arts college, and even on the local public schools.