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 rewardmotivated behaviors.

Attenuation of cocaine seeking in rats via enhancement of infralimbic cortical activity using stable step-function opsins

“…However, prior work suggests that such an approach may be effective (Liu et al 2016). As evidence suggests that the NAshell is involved in the regulation of reward seeking and is a critical projection target for the IL during the inhibition of cocaine-seeking behaviors (Augur et al 2016; Di Chiara 2002; Gorelova and Yang 1997; Kelley 2004; LaLumiere et al 2012; Ma et al 2014; Peters et al 2008), we investigated the use of SSFOs to stimulate IL terminals in the NAshell using the present behavioral paradigm.…”

“…Thus, even if the result is not spurious, the small size of the effect warrants further consideration. Although mechanisms of action regarding SSFO illumination at axonal terminals are not yet clear, studies suggest that the effects of SSFOs on terminals likely involve secondary mechanisms of neurotransmitter release, such as Ca 2 + influx (Liu et al 2016). As a consequence, the effects of activation of SSFOs in terminals may be quite different than effects on cell bodies and may not be as physiologically relevant as the SSFO-mediated activation of cell bodies, though this requires further study.…”

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

“…Experiments have demonstrated the critical role of nucleus accumbens (AcbC) in sleep control (Lazarus et al, 2012(Lazarus et al, , 2013Qiu et al, 2012;Zhang et al, 2013;Liu et al, 2016). Moreover, previous work from our laboratory has provided reliable measurements of monoamines and AD from AcbC Mijangos-Moreno et al, 2014.…”

Morphine differentially alters the synaptic and intrinsic properties of D1R- and D2R-expressing medium spiny neurons in the nucleus accumbens

“…The chronaxie was calculated, using GraphPad Prism software, as the 101 duration corresponding to 2x the rheobase, by solving for x in the equation, 102 rheobase*2=rheobase + SpanFast*exp(-KFast*x) + SpanSlow*exp(-KSlow*x). 103 For excitatory/inhibitory ratio (E/I) experiments (Liu et al, 2016), recording electrodes (2-5 MΩ) 104 were filled with a cesium-based internal solution (in mM): 135 CsMeSO3, 5 CsCl, 5 TEA-Cl,…”