MAPPING OF VAGAL-DERIVED BRAINSTEM PATHWAYS AND THEIR POTENTIAL INFLUENCE IN DOPAMINERGIC NEURON DEGENERATION USING CONVENTIONAL AND MICROBIOTA-DEFICIENT MICE

Parkinson’s disease (PD) is a complex neurodegenerative disorder, the hallmark of which is degeneration of midbrain dopaminergic neurons. There is a greater susceptibility of substantia nigra pars compacta (SNc) dopaminergic neurons over adjacent ventral tegmental area (VTA) dopaminergic neurons. Emerging evidence suggests that body-brain interactions and the microbial populations in our gut play a critical role in PD development. We are investigating the differential properties of brainstem inputs onto SNc and VTA dopaminergic neurons and the properties of these projections with respect to body and gut-vagal nerve-derived activity. Vagal neurons communicate signals from the gut to the nucleus of the solitary tract (NTS) in the brainstem, and NTS neurons project to SNc and VTA through two different intermediate brain nuclei: The parabrachial nucleus (PBN) and the paraventricular nucleus of the hypothalamus (PVN). We hypothesise that activity in these pathways plays an important role in the degeneration of dopamine neurons in PD. By combining combinatorial viral labelling and multichannel immunohistochemistry, we demonstrate that NTS projections to PVN and PBN arise from different cell populations. Secondly, our emerging findings reveal the unique molecular makeup of the NTS-PBN and NTS-PVN circuits innervating SNc- and VTA dopaminergic neurons. Thirdly, we contrast these pathways in microbiota-deficient and conventional mice in both sexes. Understanding the differential effect of vagal-derived activity on midbrain dopamine neuron populations is important for understanding the role of the gut and gut microbiome in PD progression.