Cilia mediated neuromodulation of reward pathways
Substance use disorders are a significant health issue in the US, costing tens of thousands of lives and hundreds of billions of dollars annually. The neural mechanisms that underlie substance use disorders are complex, and impacted by numerous outside factors. These additional actors include several neuromodulatory peptides that are associated with physiological states such as hunger and satiety. Within the past ten years it has been discovered that several of the receptors for these neuromodulators are enriched in the primary cilia of neurons. The goal of this research is to determine how signaling through the primary cilium contributes to integration of neuromodulatory signals that regulate responsiveness to drugs of abuse and related behaviors. We are using pharmacological and viral-mediated gene delivery approaches to study the role of cilia on GABAergic and dopaminergic neruons in regulating these behaviors. We are interested in understanding the consequences of cilia loss, particularly in the nucleus accumbens, for the rewarding effects of cocaine and morphine. In addition to using ciliary signaling to identify novel modulators of these behaviors. This project uses a variety of techniques including behavior experiments, viral manipulations, calcium imaging and microscopy. Cilia represent a unique neuronal signaling environment and a better understanding of this could lead to novel targets for therapies aimed at reducing substance use.