My work on biological neural network formation is a collaboration with Dr. Arjen Van Ooyen at the Institute of Brain Research, Graduate School Neurosciences, Amsterdam. The question we are studying is what extracellular processes are involved in biological neural network formation and the creation of topographic maps by layers of neurons. As diffusible chemoattractants and chemorepellants as well as contact attraction and contact repulsion have been implicated in the establishment of connections between neurons and their targets, it is important to understand how such diffusible and contact signals can be involved in the whole sequence of events from bundling of axons,guidance of axon bundles to their target region, to debundling and the final innervation of individual targets (see Figure). In addition, I have an interest in the sensitivity of biologically proposed mechanisms of guidance and network formation. Questions such as how noise and chemoattractant fluctuations and parameters such as the growth cone diameter and the density of receptors on the cell surface will limit the ability of a nerve fiber to perform these tasks.
Another important topic is bebundling and the formation of topographic maps. Topographic maps describe the tendency of one layer of cells (for example the retina) to map in a topographically well-defined manner to another layer of cells (for example the optic tectum). How does this occur? Our initial simulations show that though bundling and debundling can occur in a topographically ordered way so that neighbouring neurons come to innervate neighbouring target cells the mapping is weak. For example, random axon movements, which are needed for bundling in the absence of axon-derived chemoattractants, tend to disturb this pattern. Thus other types of gradients, for example gradients in receptor density on axons that are complementary to those in ligand density on target cells may be involved in the formation of topographical maps. I am investigating such biologically motivated mechanisms and their limitations by computational means.
H.G.E. Hentschel and A. Van Ooyen,Mechanisms for axon guidance and bundling during development. Proc. R. Soc. B266,2231 (1999).
H.G.E. Hentschel and A. Van Ooyen,Axon Guidance and Bundling During Neural Network Development}. (To appear Physica A, 2000).
