title: 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 (THVTA) neurons, as well as from more global maladaptation in neurocircuit function. However, whether THVTAactivity affects large-scale brain-wide function remains unknown. Here we selectively activated THVTAneurons 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 THVTAneurons 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 THVTAneuronal 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 THVTAneurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct THVTAinput.
authors: Curriculum in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.
authors: Heather K
authors: HK
authors: Decot
authors: Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.|Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Vijay M K
authors: VM
authors: Namboodiri
authors: Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Wei
authors: W
authors: Gao
authors: Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.
authors: Jenna A
authors: JA
authors: McHenry
authors: Curriculum in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.
authors: Joshua H
authors: JH
authors: Jennings
authors: Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Sung-Ho
authors: SH
authors: Lee
authors: Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.
authors: Pranish A
authors: PA
authors: Kantak
authors: Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Yu-Chieh
authors: YC
authors: Jill Kao
authors: Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Manasmita
authors: M
authors: Das
authors: Princeton Neuroscience Institute and Department of Psychology, Princeton University, Princeton, NJ, USA.
authors: Ilana B
authors: IB
authors: Witten
authors: Department of Bioengineering, Stanford University, Stanford, CA.
authors: Karl
authors: K
authors: Deisseroth
authors: Curriculum in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Yen-Yu Ian
authors: YI
authors: Shih
authors: Curriculum in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Departments of Psychiatry and Cell Biology and Physiology, Chapel Hill, NC, USA.|Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors: Garret D
authors: GD
authors: Stuber
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000502:physiology*; D059907:Functional Neuroimaging / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D017557:Ventral Tegmental Area / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D004298:Dopamine