In vivo evidence of negative fMRI response without decrease in neuronal activity: a combined optogenetic fMRI and electrophysiology study

Neurovascular coupling is the central principle of functional magnetic resonance imaging (fMRI), and thus critical for the interpretation of most fMRI data. While the strong majority of studies support such a tight coupling between neuronal and vascular activity changes in the cortex, the case may not be so straightforward in brain areas containing different cell types such as the striatum, wherein negative fMRI response has been observed to be positively correlated with1, 2, or uncorrelated with electrophysiologically-measured neuronal activity3, 4. Thus, the rodent striatum is an attractive platform to mechanistically dissect the rules governing neurovascular coupling, providing a novel case in which known coupling rules are violated. Taking this path, we began by asking a simple yet critical question: are neuronal activity increases in striatum causal in striatal negative fMRI response? Our results, employing an optogenetic-fMRI approach coupled with correlative in vivo electrophysiology, reveal that, indeed, selective excitation of striatal neurons drives large-scale local negative fMRI response. However, complementary electrophysiological data also described here suggests that the link between striatal neuronal activity and hemodynamics is more complicated than straightforward negative coupling