Historically, the central nervous system (CNS) and the immune system have been regarded as strictly separate. However, in the brain, resident macrophages, called microglia, play both immune and glial cell functions. Indeed, these cells constantly extend and retract branches to monitor neuronal activity directly. Upon contacts with neurons they have been shown to either support their functional integration or engulf apoptotic, injured and sick cells with surgical precision. How microglia sense the health status of neurons and how they respond accordingly, remains, however, largely unknown. Based on previous in vitro studies chemokines in particular have been shown to be central players in mediating neuronal microglial communication. Here, I propose to establish how chemokine mediated signals are transmitted across the brain and how in turn they are translated into functional interactions between neurons and neighboring microglia by manipulating, for the first time, one cell type to study the response of the other in real-time. To this aim, I will combine reverse genetic approaches, to manipulate neuronal gene expression under the microscope in a temporal manner, with quantitative imaging to monitor the behavior of the complete microglia network in response to neuronal signaling in a living brain. Moreover, this approach will also serve for testing the biological significance of novel factors identified in a genome-wide expression profiling approach. Ultimately, the results of this study will deepen our understanding of how diffusible signals are interpreted and translated into dynamic collective cell behaviors. There is no doubt that the scientific and complementary training that I will receive at the EMBL, will significantly contribute to my development as a mature scientist and will equip me for starting my own research group in the future.