OptoSens-fMRI of the nigrostriatal pathway

Manipulation and real-time monitoring of neuronal activity with cell-type specificity and precise spatiotemporal resolution are indispensable means to explore and expand our understanding of brain function in vivo. Simultaneous optogenetics and fiber photometry can unlock precisely that - the manipulation and measurement of neural activity and neurochemical release with high temporal resolution. Furthermore, in combination with functional magnetic resonance imaging (fMRI), locally controlled neuronal firing and its physiological effects can be readily linked to changes in global brain activity, allowing researchers to bridge functional insights across scales. In this study, we present simultaneous optogenetic stimulation and dopamine-sensing during fMRI measurements, a technique we term optoSens-fMRI, of the nigrostriatal pathway in an anaesthetized rat model. By selectively activating nigral projections in the dorsomedial striatum using the red-shifted opsin ChrimsonR, we report robust bouts of striatal dopamine release as indicated by the fluorescent indicator dLight1.1. Importantly, these events temporally correlate with fMRI signals in the targeted striatum and further engage key regions of the basal ganglia – corticothalamic pathway, including the globus pallidus and motor cortex. Our results demonstrate how optoSens-fMRI can be employed to successfully visualize and dissect the local and long-range functional impact of specific neuronal pathways on brain function in both health and disease.