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Feil Family Brain & Mind Research Institute

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Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior.

TitlePrefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior.
Publication TypeJournal Article
Year of Publication2016
AuthorsFerenczi EA, Zalocusky KA, Liston C, Grosenick L, Warden MR, Amatya D, Katovich K, Mehta H, Patenaude B, Ramakrishnan C, Kalanithi P, Etkin A, Knutson B, Glover GH, Deisseroth K
Date Published2016 Jan 01
KeywordsAnhedonia, Animals, Brain Mapping, Corpus Striatum, Depressive Disorder, Dopamine, Dopaminergic Neurons, Female, Magnetic Resonance Imaging, Male, Mesencephalon, Motivation, Nerve Net, Oxygen, Prefrontal Cortex, Rats, Rats, Inbred LEC, Rats, Sprague-Dawley, Reward, Schizophrenia

Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions.

Alternate JournalScience
PubMed ID26722001
PubMed Central IDPMC4772156
Grant List1F31MH105151_01 / MH / NIMH NIH HHS / United States
P41 EB015891 / EB / NIBIB NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
DP2 MH109982 / MH / NIMH NIH HHS / United States
R00 MH097822 / MH / NIMH NIH HHS / United States
R37 DA035377 / DA / NIDA NIH HHS / United States
R01 MH086373 / MH / NIMH NIH HHS / United States
F31 MH105151 / MH / NIMH NIH HHS / United States
R01 DA035377 / DA / NIDA NIH HHS / United States