Functional PET/MRI reveals active inhibition of neuronal activity during optogenetic activation of the nigrostriatal pathway

The dopaminergic system is a central component of the brain's neurobiological framework, governing motor control, reward responses, and playing an essential role in various brain disorders. Within this complex network, the nigrostriatal pathway represents a critical circuit for dopamine neurotransmission from the substantia nigra to the striatum. However, stand-alone functional magnetic resonance imaging (fMRI) is unable to study the intricate interplay between brain activation and its molecular underpinnings. In our study, the use of a functional [18F]FDG positron emission tomography (fPET) approach simultaneously with blood oxygen level-dependent (BOLD)-fMRI provided an important insight that demonstrates an active suppression of the nigrostriatal activity during optogenetic stimulation. This result increases our understanding of the molecular mechanisms of brain function and provides an important perspective on how dopamine influences hemodynamic responses in the brain.

Methods
All the data collection and processing steps are described in the manuscript and supplemental notes.