Defensive state mechanisms in Parkinson’s disease

Freezing of gait (FoG) is a severely debilitating motor symptom of Parkinson’s disease (PD) that currently lacks optimal treatment options. Anxiety has been associated with severity of FoG in PD, which is further affected by stress and emotional situations. In rodents, fear-induced freezing involves disinhibitory circuit mechanisms in the periaqueductal gray (PAG, Tovote et al. 2016), a midbrain structure where emotional and (pre-)motor circuits converge. As part of the Collaborative Research Centre TRR 295 ReTune, we investigate how the loss of monoaminergic neuromodulation during PD alters PAG activity, thereby contributing to locomotor dysfunction during fear and anxiety states. Using a mouse model of synucleinopathy in combination with optogenetic, electrophysiological, and imaging techniques, we characterize the neuroarchitecture and function of brainstem circuits throughout the pathophysiology of PD to understand its effects on motor- and anxiety-related behavior. Ultimately, we aim at combining neuronal activity and kinematic parameters with behavioral and cardiac measurements to get an integrated understanding of the PD pathostate.