Neurovascular Coupling in the Dorsal Striatum

Since its introduction in the late 1980s, functional magnetic resonance imaging (fMRI) has become a widely used tool to study human brain function and networks. fMRI gives an indirect measure of neuronal activity and its data are therefore interpreted according to the presumed relationship between neuronal and vascular responses, often termed as neurovascular coupling (NVC). In essence, NVC suggests that regional neuronal and hemodynamic activities are scalable under physiological conditions. However, NVC may not be regulated uniformly throughout the brain, and thus may complicate fMRI data interpretation. Deciphering the mechanisms behind regional NVC differences is of paramount importance as the number of fMRI studies rises. The dorsal striatum, or the caudate putamen (CPu) in the rodent brain, represents a brain region with distinct neuronal composition and neurochemical transmission as compared to the cerebral cortex. We performed a comprehensive dissection of fMRI signal sources in the rat striatum to better understand the origin of its responses. We performed optogenetic-fMRI of several distinct circuits related to the striatum, recorded electrophysiological signals, measured dopamine (DA) release, manipulated neurotransmission using concurrent intracranial pharmacology and fMRI, performed multispectral fiber-photometry to assess striatal neurovascular coupling, and finally, conducted human fMRI studies with our collaborators. Our results suggest revising interpretation of positive fMRI responses in the striatum from neuronal activation to DA release, and negative fMRI responses in the striatum from neuronal inhibition to activation and opioidergic neurotransmission. These findings may help interpret fMRI signals in other brain areas with atypical NVC, and more broadly to neuroimaging techniques using vascular responses as a surrogate for neuronal activity.