Unlike the vast supercomputers housed in large rooms, the brain is caged within a relativity small cavity under the skull. Yet, the brain's processing capabilities still surpass those in even the fastest supercomputers. Some have claimed that one million Pentium processors would be needed to generate the same information conveyed in just a single second of synaptic activity in the brain. True or not, what individual neurons in the brain accomplish in such a tiny space is remarkable simply by forming numerous synaptic pairings with the fine network of dendritic branches extending out from other neurons. The beauty and complexity of these networks is fascinating. Our laboratory wants to know how a neuron's cyto-architecture can build such astonishing interconnected structures with other neurons.
Newly formed cells in a developing brain will migrate to their target destination to become cortical neurons. Santiago Ramón y Cajal first observed the role of cell migration in the developing brain more than a century ago. His work still motivates many brain scientists. However, the traditional method for observing brain development, namely fixed brain samples illuminated under a microscope, could not provide insight into the mechanisms that enabled cell migration. Innovations in this century have only just made detailed observations of living neuron migration possible. Newly exposed phenomena are starting to challenge long held theories about the routes and mechanisms that drive cell migration.
Our laboratory is now studying the migration of granule cells, neurons found in the cerebellum using a technique we developed that reproduces cell migration in vivo. We place a thick slice of brain, thick enough to retain cerebellar tissue, in a culture dish and observe cells in the sample over time using a confocal microscope. In this way, we have clarified part of the molecular mechanism of forward transport of nuclei of these cells. Next, we would like to determine those molecules that feed the motive force of migration.
We also want to know how the branching pattern of dendrites is determined. The dendrites of a Purkinje cell can form synapses with more than 20,000 granule cells. To make this possible in such a confined space, the dendrites extend out and up like a fan, intersecting with the axons of granule cells running horizontally to make as many connections as possible. The multiple connections with various cells made by Purkinje cells may explain why the dendrites of these neurons have developed a planar structure. Further analysis of this process in vivo would clarify this point. At present, we are trying to elucidate the dynamics of dendritic branching in the brain during development and the inter-cellular interactions that determine those patterns.
