Measuring and modelling the dynamics of retinotopic map formation. (360G-Wellcome-083205_B_07_Z)

It is not known how axons are guided to make appropriate connections at their target. We examine the paradigm case of the ordered map of connections between vertebrate retina onto contralateral superior colliculus (or optic tectum). We aim to understand how signalling cues arising from neuronal activity and from specific molecules interact to form this map. We will integrate our expertise in computational modelling with electrophysiological mapping and quantitative molecular techniques. The a nimal of choice is the mouse, in which it is possible to measure connectivity patterns resulting from disturbance, by genetic means, of activity-based and/or molecular-based signalling. Using contemporary imaging techniques, we will visualise the connectivity patterns formed at a resolution that is sufficiently high to enable us to develop a biologically-realistic quantitative computational model that will guide our experiments. To achieve our goals, we will trace the development of the mapp ing in wild-type mouse and in selected mutants; these results together with data from the literature will be used to constrain our model of this dynamic process, which will incorporate both activity-based and molecular signalling mechanisms; the model will be tested on our data from a more complex set of mutants.