Description:

Nicole Calakos MD PhD

Professor of Neurology, Neurobiology and Cell Biology

Duke University Medical Center

Cell stress response pathways like the unfolded protein response (UPR) and integrated stress response (ISR) are typically thought of as conditional, on-demand responses to intermittent perturbations that are recruited to restore cell homeostasis. I will discuss recent insights Kozorovitskiyenabled by genetic reporters that reveal a new normal relationship with such pathways in neuromodulatory neurons. In certain classes of cholinergic and dopaminergic neurons, the ISR proteostasis pathway is constitutively active under healthy brain conditions. I will discuss how disruptions to ISR activation modify neuronal activity, dopamine signaling, and behavior and the implications this property may carry for diseases like dystonia and Parkinson’s.  Finally, I will introduce reagents and a mouse model of the SPOTlight reporter that provide opportunities to uncover hidden aspects of ISR regulation in other cell types and settings.