Gaining Access to Sox6+ SNpc Dopamingergic Neurons

The debilitating motor symptoms associated with Parkinson’s disease (PD) are largely caused by selective degeneration of dopaminergic (mDA) neurons located in the substantia nigra pars compacta (SNpc) [1]. This neuronal population therefore, is a key cellular substrate underpinning PD, and therefore of immense significance. Despite the clinical importance of this neuronal population, there is a complete lack of available genetic tools to analyze their biology. Thus, while modern conditional mouse genetics has been used to manipulate scores of neuronal populations yielding groundbreaking results [2-5], this key neuronal population has remained refractory to specific genetic manipulation. The missing key element in the toolbox is a pan-SNpc recombinase driver. Here, rationally guided by single cell DA neuron profiling analyses, we propose to generate recombinase drivers that will allow conditional genetic manipulations specifically in the SNpc. These genetic tools are invaluable for studying the molecular properties of SNpc DA neurons as well as generating additional models of PD.