Prefrontal cortex to accumbens projections in sleep regulation of reward
Open accessAbstract
UNLABELLED: 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. SIGNIFICANCE STATEMENT: 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.
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Animal studies have recapitulated the phenomenon of sleep loss-enhanced reward seeking observed in humans.
“animal studies have recapitulated the phenomenon of sleep loss-enhanced reward seeking observed in humans.”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [100]
Acute sleep deprivation or chronic partial sleep restriction in animals often leads to enhanced risk taking and reward seeking, including cocaine and alcohol intake, sucrose self-administration, and intracranial self-stimulation.
“Acute sleep deprivation or chronic partial sleep restrictions in animals often leads to enhanced risk taking and reward seeking, including cocaine and alcohol intake, sucrose self-administration, as well as intra-cranial self-stimulations (99–103).”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [100]
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Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents
Logan, R. W., Hasler, B. P., Forbes, E. E., Franzen, P. L., Torregrossa, M. M., Huang, Y. H., Buysse, D. J., Clark, D. B., & McClung, C. A. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.035 · Cited by 194 · see citing works
Self-citationWood, J., LaPalombara, Z., & Ahmari, S. E. (2018) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2017.0023 · Cited by 41 · see citing works
- Authors
- Liu, Z., Wang, Y., Cai, L., Li, Y., Chen, B., Dong, Y., & Huang, Y. H.
- Affiliations
- University of Pittsburgh (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2016-07-27
- Volume
- 36
- Issue
- 30
- Pages
- 7897-7910
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4961777
- OpenAlex
- W2505475551
- Cited by
- 66
- References
- 106
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 5 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 3 · 2016: 1
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH101147)
- National Institute on Drug Abuse (R01DA030379, R01DA023206, K99DA029565, R01DA035805, R00DA029565, R01DA034856, R01DA040620, R37DA023206)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- sleep deprivation, reward seeking, medial prefrontal cortex, nucleus accumbens, glutamatergic neurotransmission, synaptic inhibition, sucrose seeking, optogenetics
- MeSH terms
- Animals, Behavior, Animal, Eating, Male, Mice, Inbred C57BL, Neural Pathways, Neuronal Plasticity, Nucleus Accumbens, Reward, Sleep, Sleep Deprivation, Prefrontal Cortex, Feedback, Physiological, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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