PROJECT: JTC2009: ImageNinND

The olfactory bulb (OB), showing characteristic pathological changes early on within Parkinson?s disease (PD) on the one hand and strong capacity of adult neurogenesis throughout lifetime on the other hand is the ideal brain region to analyse the potential benefit of approaches aiming to rescue neuronal cell loss via adult neurogenesis. Due to the superficial location of the olfactory bulb in the rodent brain there is the unique opportunity to study the integration of newborn neurons into pathologically affected brain circuits in the living animal. By the use of the cranial window technique and two-photon (2P) imaging we will investigate dendritogenesis and synaptogenesis of dopaminergic adult-born neurons within the OB of transgenic animal models of PD for the first time. Moreover, we aim to identify cell-autonomous factors, which have a potential impact on these processes in vivo via siRNA knockdown and overexpression of candidate factors. In addition we will study the role of neuronal activity in synapse formation and stability of adult-born neurons in wild type mice and transgenic mouse models of PD using a new technique of light-driven control of neuronal excitability. With the help of these new techniques we aim to elucidate the mechanisms of functional integration of adult-born neurons under physiological conditions and of reduced survival of adult-born neurons in the olfactory bulb of transgenic mouse models of PD, which may help to identify new targets for PD therapy.