Dopamine neurons: Subtypes, microenvironment, and regenerative potential

Midbrain dopamine (mDA) neurons play essential roles in diverse neural processes and degenerate in Parkinson’s disease (PD). Our studies address key questions concerning the development and diversity of these neurons. Very little is known of how neural stem cells giving rise to mDA neurons transition into quiescent ependymal cells.

Building on previous VR-supported research we will investigate induction of quiescence by focusing on an intriguing population of mDA progenitor-derived adult midbrain ependymal cells with radial glia/stem cell properties.

These studies will explain essential regulation of quiescence, with implications for stem cell therapy, and may indicate new strategies for inducing mDA neuron regeneration in the adult. In additional experiments we will investigate mDA neuron diversity. New methods for single cell RNA sequencing have revolutionized studies of cellular diversity.

A refined strategy adapted to efficiently dissociate and sequence mDA neuron nuclei will be used to acquire a detailed molecular understanding of mDA neuron subtypes, including those that degenerate in PD.

Moreover, we will extend the analysis to neighboring cell types, and investigate consequences of mDA neuron stress in PD rodent models.

This will resolve the molecular and anatomical architecture of mDA neuron subtypes and their microenvironment, providing invaluable opportunities for new discoveries of major significance for understanding mDA neuron physiology and disease.