title: Prefrontal Cortex to Accumbens Projections in Sleep Regulation of Reward.
abstract: Sleep profoundly affects the emotional and motivational state. In humans and animals, loss of sleep often results in enhanced motivation for reward, which has direct implications for health risks as well as potential benefits. Current study aims at understanding the mechanisms underlying sleep deprivation (SDe)-induced enhancement of reward seeking. We found that after acute SDe, mice had an increase in sucrose seeking and consumption but not food intake, suggesting a selective enhancement of motivation for reward. In the nucleus accumbens (NAc), a key brain region regulating emotional and motivational responses, we observed a decrease in the ratio of the overall excitatory over inhibitory synaptic inputs onto NAc principle neurons after SDe. The shift was partly mediated by reduced glutamatergic transmission of presynaptic origin. Further analysis revealed that there was selective reduction of the glutamate release probability at the medial prefrontal cortex (mPFC)-to-NAc synapses, but not those from the hippocampus, thalamus, or the basal lateral amygdala. To reverse this SDe-induced synaptic alteration, we expressed the stabilized step function opsin (SSFO) in the mPFC; optogenetic stimulation of SSFO at mPFC-to-NAc projection terminals persistently enhanced the action potential-dependent glutamate release. Intra-NAc optogenetic stimulation of SSFO selectively at mPFC-to-NAc terminals restored normal sucrose seeking in mice after SDe without affecting food intake. These results highlight the mPFC-to-NAc projection as a key circuit-based target for sleep to regulate reward-motivated behaviors.
  
  
  
  Sleep loss, a costly challenge of modern society, has profound physiological and psychological consequences, including altered reward processing of the brain. The current study aims at understanding the mechanisms underlying sleep deprivation-induced enhancement of reward seeking. We identify that the medial prefrontal cortex (mPFC)-to-nucleus accumbens (NAc) glutamatergic transmission is selectively weakened following acute sleep deprivation, whose restoration normalizes reward seeking in sleep-deprived mice. These results suggest a possibility of normalizing sleep deprivation-induced abnormal reward seeking by targeting specific neural projections, and they demonstrate the mPFC-to-NAc glutamatergic projection as a key circuit-based target for sleep to regulate reward-motivated behaviors.
authors.affiliation: Departments of Psychiatry and.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15219.
authors.forename: Yao
authors.identifier: 0000-0002-1855-6280
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Departments of Psychiatry and.
authors.forename: Li
authors.identifier: 0000-0002-1389-6892
authors.initials: L
authors.lastname: Cai
authors.affiliation: Departments of Psychiatry and.
authors.forename: Yizhi
authors.identifier: 0000-0002-8795-6528
authors.initials: Y
authors.lastname: Li
authors.affiliation: Departments of Psychiatry and.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Departments of Psychiatry and Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15219.
authors.forename: Yan
authors.identifier: 0000-0003-0016-9028
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Departments of Psychiatry and yhhuang@pitt.edu.
authors.forename: Yanhua H
authors.identifier: 0000-0003-1770-0196
authors.initials: YH
authors.lastname: Huang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004435:Eating; D025461:Feedback, Physiological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012201:Reward; D012890:Sleep; D012892:Sleep Deprivation / Q000503:physiopathology*
keywords: SSFO; accumbens; mPFC; reward; self-administration; sleep