Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons.

Abstract Several neuropsychiatric conditions, such as addiction and schizophrenia may arise in part from dysregulated activity of ventral tegmental area dopaminergic (TH(VTA)) neurons, as well as from more global maladaptation in neurocircuit function. However, whether TH(VTA) activity affects large-scale brain-wide function remains unknown. Here, we selectively activated TH(VTA) neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging (fMRI). Applying a standard generalized linear model (GLM) analysis approach, our results indicate that selective optogenetic stimulation of TH(VTA) neurons enhanced cerebral blood volume (CBV) signals in striatal target regions in a dopamine receptor dependent fashion. However, brain-wide voxel-based principal component analysis (PCA) of the same dataset revealed that dopaminergic modulation activates several additional anatomically distinct regions throughout the brain, not typically associated with dopamine release events. Furthermore, explicit pairing of TH(VTA) neuronal activation with a forepaw stimulus of a particular frequency expanded the sensory representation of that stimulus, not exclusively within the somatosensory cortices, but brain-wide. These data suggest that modulation of TH(VTA) neurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct TH(VTA) input.Neuropsychopharmacology accepted article preview online, 12 August 2016. doi:10.1038/npp.2016.151.