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000139981 037__ $$aDZNE-2020-06303
000139981 041__ $$aEnglish
000139981 082__ $$a610
000139981 1001_ $$0P:(DE-HGF)0$$aBrocka, Marta$$b0
000139981 245__ $$aContributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits.
000139981 260__ $$aOrlando, Fla.$$bAcademic Press$$c2018
000139981 264_1 $$2Crossref$$3print$$bElsevier BV$$c2018-08-01
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000139981 520__ $$aMapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful interpretation of reward-related human fMRI data.
000139981 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
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000139981 650_7 $$2NLM Chemicals$$aDopamine Antagonists
000139981 650_7 $$0VTD58H1Z2X$$2NLM Chemicals$$aDopamine
000139981 650_2 $$2MeSH$$aAnimals
000139981 650_2 $$2MeSH$$aBehavior, Animal: physiology
000139981 650_2 $$2MeSH$$aBrain: diagnostic imaging
000139981 650_2 $$2MeSH$$aBrain: metabolism
000139981 650_2 $$2MeSH$$aBrain: physiology
000139981 650_2 $$2MeSH$$aDopamine: metabolism
000139981 650_2 $$2MeSH$$aDopamine Antagonists: pharmacology
000139981 650_2 $$2MeSH$$aDopaminergic Neurons: physiology
000139981 650_2 $$2MeSH$$aElectric Stimulation
000139981 650_2 $$2MeSH$$aElectrodes, Implanted
000139981 650_2 $$2MeSH$$aGenetic Vectors
000139981 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000139981 650_2 $$2MeSH$$aNeurons: metabolism
000139981 650_2 $$2MeSH$$aNeurons: physiology
000139981 650_2 $$2MeSH$$aNeurovascular Coupling: physiology
000139981 650_2 $$2MeSH$$aOptogenetics
000139981 650_2 $$2MeSH$$aRats
000139981 650_2 $$2MeSH$$aRats, Long-Evans
000139981 650_2 $$2MeSH$$aRats, Transgenic
000139981 650_2 $$2MeSH$$aRats, Wistar
000139981 650_2 $$2MeSH$$aReward
000139981 650_2 $$2MeSH$$aSelf Stimulation: physiology
000139981 650_2 $$2MeSH$$aStereotaxic Techniques
000139981 650_2 $$2MeSH$$aTomography, Emission-Computed, Single-Photon
000139981 650_2 $$2MeSH$$aVentral Tegmental Area: diagnostic imaging
000139981 650_2 $$2MeSH$$aVentral Tegmental Area: metabolism
000139981 650_2 $$2MeSH$$aVentral Tegmental Area: physiology
000139981 7001_ $$0P:(DE-2719)2811369$$aHelbing, Cornelia$$b1$$udzne
000139981 7001_ $$0P:(DE-HGF)0$$aVincenz, Daniel$$b2
000139981 7001_ $$0P:(DE-HGF)0$$aScherf, Thomas$$b3
000139981 7001_ $$0P:(DE-HGF)0$$aMontag, Dirk$$b4
000139981 7001_ $$0P:(DE-HGF)0$$aGoldschmidt, Jürgen$$b5
000139981 7001_ $$0P:(DE-2719)2810456$$aAngenstein, Frank$$b6$$udzne
000139981 7001_ $$0P:(DE-HGF)0$$aLippert, Michael$$b7$$eCorresponding author
000139981 77318 $$2Crossref$$3journal-article$$a10.1016/j.neuroimage.2018.04.059$$b : Elsevier BV, 2018-08-01$$p88-97$$tNeuroImage$$v177$$x1053-8119$$y2018
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