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Prefrontal Cortex to Accumbens Projections in Sleep Regulation of Reward
Liu Z, Wang Y, Cai L, Li Y, Chen B, Dong Y, and Huang YH
Journal of Neuroscience, Published online, 2016

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. 

Dr. Yanhua Huang and her colleagues investigated the mechanisms underlying sleep deprivation (SDe)-induced enhancement of reward seeking. They 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, the investigators 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, they 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. Finally, 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 suggest a possibility of normalizing sleep deprivation-induced abnormal reward seeking by targeting specific neural projections, and they highlight the mPFC-to-NAc glutamatergic projection as a key circuit-based target for sleep to regulate reward-motivated behaviors.

Contributors:
Zheng Liu,PhD, Cai Li, Yizhi Li, Bo Chen, PhD, Yan Dong, PhD, and Yanhua H. Huang, PhD (Department of Psychiatry, University of Pittsburgh)

Yao Wang, PhD, Yan Dong, PhD (Department of Neuroscience, University of Pittsburgh) 

This article was published online in the Journal of Neuroscience. To view the abstract, click here.