title: Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior.
abstract: 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.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.|Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Ferenczi
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.|Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Zalocusky
authors.affiliation: Brain Mind Research Institute, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.|Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Logan
authors.initials: L
authors.lastname: Grosenick
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Warden
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Debha
authors.initials: D
authors.lastname: Amatya
authors.affiliation: Department of Psychology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Kiefer
authors.initials: K
authors.lastname: Katovich
authors.affiliation: Department of Psychology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Hershel
authors.initials: H
authors.lastname: Mehta
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Patenaude
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Charu
authors.initials: C
authors.lastname: Ramakrishnan
authors.affiliation: Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Kalanithi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Etkin
authors.affiliation: Department of Psychology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Knutson
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Glover
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.|Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA.|Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
mesh_terms: D059445:Anhedonia / Q000502:physiology*; D000818:Animals; D001931:Brain Mapping; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003866:Depressive Disorder / Q000503:physiopathology; D004298:Dopamine / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009042:Motivation; D009415:Nerve Net / Q000502:physiology; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020332:Rats, Inbred LEC; D017207:Rats, Sprague-Dawley; D012201:Reward; D012559:Schizophrenia / Q000503:physiopathology
chemical_list: D010100:Oxygen; D004298:Dopamine