Assessing the function of a dopamine neuron subtype that is vulnerable in PD

The midbrain dopaminergic neurons (DA) are involved in diverse physiological pathways including motor control, cognition, and reward behaviors. These neurons are clustered in three anatomically defined areas: the substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA) and the retrorubral area (RRA). In the last twenty years, several lines of evidence have suggested that there may be additional levels of DA heterogeneity, based on distinct molecular signature, physiology, and connectivity, that may be even more meaningful than their classification into three anatomically defined clusters. Particularly relevant to Parkinson’s Disease (PD), the ventral tier of the SNpc neurons are specifically lost in PD patients, whereas VTA and the retrorubral area are selectively spared. Further understanding of dopaminergic diversity, would enhance our understanding of selective dopamine neuron vulnerability in PD. In the previous year, the Ruby foundation funded a project in my lab to uncover the embryonic basis of DA diversity. In this year of funding, we aim to develop a set of novel, noninvasive, genetic tools to begin to uncover the functional aspects of dopaminergic neuron diversity in the adult.