Consolidation of Reward Memory during Sleep Does Not Require Dopaminergic Activation

Sleep enhances memories, especially if they are related to future rewards. Although dopamine has been shown to be a key determinant during reward learning, the role of dopaminergic neurotransmission for amplifying reward-related memories during sleep remains unclear. In this study, we scrutinize the idea that dopamine is needed for the preferential consolidation of rewarded information. We impaired dopaminergic neurotransmission, thereby aiming to wipe out preferential sleep-dependent consolidation of high- over low-rewarded memories during sleep. Following a double-blind, balanced, crossover design, 17 young healthy men received the dopamine d2-like receptor blocker sulpiride (800 mg) or placebo, after learning a motivated learning task. The task required participants to memorize 80 highly and 80 lowly rewarded pictures. Half of them were presented for a short (750 msec) and a long (1500 msec) duration, respectively, which permitted dissociation of the effects of reward on sleep-associated consolidation from those of mere encoding depth. Retrieval was tested after a retention interval of approximately 22 hr that included 8 hr of nocturnal sleep. As expected, at retrieval, highly rewarded memories were remembered better than lowly rewarded memories, under placebo. However, there was no evidence for an effect of reducing dopaminergic neurotransmission with sulpiride during sleep on this differential retention of rewarded information. This result indicates that dopaminergic activation likely is not required for the preferential consolidation of reward-associated memory. Rather, it appears that dopaminergic activation only tags such memories at encoding for intensified reprocessing during sleep.

A Whole-Brain Map and Assay Parameter Analysis of Mouse VTA Dopaminergic Activation

Ascending dopaminergic projections from neurons located in the Ventral Tegmental Area (VTA) are key to the etiology, dysfunction, and control of motivation, learning, and addiction. Due to evolutionary conservation of this nucleus and the extensive use of mice as disease models, establishing an assay for VTA dopaminergic signalling in the mouse brain is crucial for the translational investigation of neuronal function phenotypes of diseases and interventions. In this article we use optogenetic stimulation for VTA dopaminergic neuron stimulation, in combination with functional Magnetic Resonance Imaging (fMRI), a method widely used in human deep brain imaging. We present the first whole-brain opto-fMRI map of dopaminergic activation in the mouse, and show that VTA dopaminergic system function is consistent with but diverges in a few key aspects from its structure. While the activation map predominantly includes and excludes target areas according to their relative projection densities (e.g. strong activation of the nucleus accumbens and low activation of the hippocampus), it also includes areas for which a structural connection is not well established (such as the dorsomedial striatum). We further detail assay variability with regard to multiple experimental parameters, including stimulation protocol and implant position, and provide detailed evidence-based recommendations for assay reuse.

Consolidation of reward memory during sleep does not require dopaminergic activation

Sleep enhances memories, especially, if they are related to future rewards. Although dopamine has been shown to be a key determinant during reward learning, the role of dopaminergic neurotransmission for amplifying reward-related memories during sleep remains unclear. In the present study, we scrutinize the idea that dopamine is needed for the preferential consolidation of rewarded information. We blocked dopaminergic neurotransmission, thereby aiming to wipe out preferential sleep-dependent consolidation of high over low rewarded memories during sleep. Following a double-blind, balanced, crossover design 20 young healthy men received the dopamine d2-like receptor blocker Sulpiride (800 mg) or placebo, after learning a Motivated Learning Task. The task required participants to memorize 80 highly and 80 lowly rewarded pictures. Half of them were presented for a short (750 ms) and a long duration (1500 ms), respectively, which enabled to dissociate effects of reward on sleep-associated consolidation from those of mere encoding depth. Retrieval was tested after a retention interval of 20 h that included 8 h of nocturnal sleep. As expected, at retrieval, highly rewarded memories were remembered better than lowly rewarded memories, under placebo. However, there was no evidence for an effect of blocking dopaminergic neurotransmission with Sulpiride during sleep on this differential retention of rewarded information. This result indicates that dopaminergic activation is not required for the preferential consolidation of reward-associated memory. Rather it appears that dopaminergic activation only tags such memories at encoding for intensified reprocessing during sleep.