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Neuropsychopharmacology. 2017 Feb;42(3):615-627. doi: 10.1038/npp.2016.151. Epub 2016 Aug 12.

Coordination of Brain-Wide Activity Dynamics by Dopaminergic Neurons.

Author information

1
Curriculum in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
2
Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.
3
Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
4
Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
5
Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
6
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
7
Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, NJ, USA.
8
Department of Bioengineering, Stanford University, Stanford, CA.
9
Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

Several neuropsychiatric conditions, such as addiction and schizophrenia, may arise in part from dysregulated activity of ventral tegmental area dopaminergic (THVTA) neurons, as well as from more global maladaptation in neurocircuit function. However, whether THVTA activity affects large-scale brain-wide function remains unknown. Here we selectively activated THVTA neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging. Applying a standard generalized linear model analysis approach, our results indicate that selective optogenetic stimulation of THVTA neurons enhanced cerebral blood volume signals in striatal target regions in a dopamine receptor-dependent manner. However, brain-wide voxel-based principal component analysis of the same data set revealed that dopaminergic modulation activates several additional anatomically distinct regions throughout the brain, not typically associated with dopamine release events. Furthermore, explicit pairing of THVTA 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 THVTA neurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct THVTA input.

PMID:
27515791
PMCID:
PMC5240174
DOI:
10.1038/npp.2016.151
[Indexed for MEDLINE]
Free PMC Article

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