Targeting the vaso-intestinal peptidergic system to decrease anxiety in Parkinson's disease

The degeneration of dopamine neurons of the substantia nigra pars compacta is well-known in motor symptoms of Parkinson’s disease (PD). However, other dopaminergic populations degenerate and give rise to non-motor symptoms such as anxiety which has a high prevalence in PD patients and strongly affects quality of life. One of these structures, the dorsal raphe nucleus (DRN), has been identified as a potential structure involved in anxiety and depression in PD. Indeed, the dopaminergic neurons of the DRN degenerate in PD, and a part of them co-releases the vaso-intestinal peptide (VIP) onto two anxiety hubs of the brain: the oval nucleus of the bed nucleus of the stria terminalis (ovBNST) and the central nucleus of the amygdala (CeA). In this study, using innovative neurotechniques we anatomically and functionally characterize this sub-population of DRN dopaminergic neurons co-expressing VIP in physiological condition. In situ hybridization experiments allowed us to characterize the molecular phenotype of the DA/VIP neurons of the DRN. Furthermore, by using a VIP-Cre transgenic mouse line associated with viral strategies we are able to identify the projections of these neurons as well as their function. Preliminary results in VIP-Cre mice in which DRNVIP neurons were genetically ablated suggest a role of these neurons in adapted responses to threatening cues. Further experiments are necessary to better understand the role of these neurons in anxiety-related behaviors and their potential implication in PD symptoms.