fMRI detects bilateral brain network activation following unilateral chemogenetic activation of direct striatal projection neurons

Although abnormal structural and functional connectivity in the striatum during neurological disorders has been reported using functional magnetic resonance imaging (fMRI), the effects of cell-type specific neuronal stimulation on fMRI and related behavioral alterations are not well understood. In this study, we successfully combined DREADD-technology with fMRI (chemo-fMRI) to investigate the alterations of spontaneous neuronal activity induced by the unilateral activation of dopamine D1 receptor-expressing neurons (D1-neurons) in the mouse dorsal striatum (DS). We compared the effects of two different DREADD ligands, clozapine (CLZ) and clozapine-N-oxide (CNO), on behavior and fMRI. We found that the effects of CLZ on behavior were more rapid than those of CNO. In fMRI, both systemic CLZ and CNO administrations, which evoked unilateral activations of D1-neurons in DS, increased the fractional amplitude of low frequency fluctuations (fALFF) in the thalamus and bilateral cortex. In addition, we found the increased gamma-band of local field potentials in DS and bilateral cortex after CLZ-evoked unilateral activation of D1-neuron in the striatum. These results provide bases for better interpretation of cell type-specific activity changes in fMRI.