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

Science. 2016 Jan 1;351(6268):aac9698. doi: 10.1126/science.aac9698.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anhedonia / physiology*
  • Animals
  • Brain Mapping
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Depressive Disorder / physiopathology
  • Dopamine / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology*
  • Female
  • Magnetic Resonance Imaging
  • Male
  • Mesencephalon / cytology
  • Mesencephalon / drug effects
  • Mesencephalon / physiology
  • Motivation*
  • Nerve Net / physiology
  • Oxygen / blood
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Inbred LEC
  • Rats, Sprague-Dawley
  • Reward*
  • Schizophrenia / physiopathology

Substances

  • Oxygen
  • Dopamine