Intersectional Genetic Approaches for Studying Dopaminergic Subpopulations

Abstract

Midbrain dopamine neurons project to numerous targets throughout the brain to modulate various behaviors and brain states. Within this small population of neurons exists significant heterogeneity based on circuitry, physiology, and disease susceptibility. Recent studies have shown that dopamine neurons can be subdivided based on gene expression; however, the extent to which genetic markers define functionally relevant dopaminergic sub‐types has not been determined. To address this, we performed single cell RNA‐sequencing of midbrain dopamine neurons and identified genes that define dopaminergic subpopulations. Using a combination of anatomy, circuit tracing, and electrophysiology we have defined the projection targets, cellular properties, and disease vulnerability of two groups of dopamine neurons. Our current efforts are aimed at generating intersectional mouse genetic tools that will allow us to selectively target and manipulate dopaminergic subpopulations to understand their functional roles. This approach will allow us to dissect the complexity of the dopaminergic system, thereby furthering our understanding of how specific dopaminergic circuits control behavior in both normal and disease states.Support or Funding InformationThis work is supported by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation and a fellowship from the Alfred P. Sloan Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.