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Review
. 2015 Aug 18;22(9):452-60.
doi: 10.1101/lm.037317.114. Print 2015 Sep.

Reward processing by the dorsal raphe nucleus: 5-HT and beyond

Affiliations
Review

Reward processing by the dorsal raphe nucleus: 5-HT and beyond

Minmin Luo et al. Learn Mem. .

Abstract

The dorsal raphe nucleus (DRN) represents one of the most sensitive reward sites in the brain. However, the exact relationship between DRN neuronal activity and reward signaling has been elusive. In this review, we will summarize anatomical, pharmacological, optogenetics, and electrophysiological studies on the functions and circuit mechanisms of DRN neurons in reward processing. The DRN is commonly associated with serotonin (5-hydroxytryptamine; 5-HT), but this nucleus also contains neurons of the neurotransmitter phenotypes of glutamate, GABA and dopamine. Pharmacological studies indicate that 5-HT might be involved in modulating reward- or punishment-related behaviors. Recent optogenetic stimulations demonstrate that transient activation of DRN neurons produces strong reinforcement signals that are carried out primarily by glutamate. Moreover, activation of DRN 5-HT neurons enhances reward waiting. Electrophysiological recordings reveal that the activity of DRN neurons exhibits diverse behavioral correlates in reward-related tasks. Studies so far thus demonstrate the strong power of DRN neurons in reward signaling and at the same time invite additional efforts to dissect the roles and mechanisms of different DRN neuron types in various processes of reward-related behaviors.

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Figures

Figure 1.
Figure 1.
Neuron types in the DRN and the connectivity of 5-HT neurons. (A) A cartoon shows the distribution of 5-HT, glutamate, GABA and dopamine neurons in the DRN. Note that some neurons express markers for both 5-HT and glutamate. (B) Input and output patterns of DRN 5-HT neurons. (mPFC) medial prefrontal cortex, (OFC) orbitofrontal cortex, (VP) ventral pallidum, (NAc) nucleus Accumbens, (LHb) lateral Habenula, (BST) bed nucleus of the stria terminalis, (CeM) central amygdala, (LH) lateral hypothalamus, (DRN) dorsal raphe nucleus, (VTA) ventral tegmental area, (SNc) substantia nigra pars compacta, (RMTg) rostromedial tegmental nucleus, and (LDT) laterodorsal tegmental nucleus.
Figure 2.
Figure 2.
Both glutamate and 5-HT contribute to reward signaling of DRN Pet-1 neurons. (A) Plots of cumulative active nose-pokes of mice showing that optogenetic stimulation of DRN Pet-1 neurons supports strong self-administration of light involving a fixed ratio 1:1 (FR1) schedule. Deleting the gene encoding VGluT3 but not Tph2 substantially reduces the effectiveness of light stimulation. (B) Genetic deletion of Tph2 drastically reduces animal performance in a test involving FR8 schedule, which requires mice making eight active pokes to receive light delivery into the DRN. Adopted from Liu et al. 2014 with permission.
Figure 3.
Figure 3.
The activity pattern of a DRN Pet-1 neuron from a behaving mouse engaged in a cue-reward association task. Peristimulus time histogram shows the spike firing rate of the DRN Pet-1 neuron identified with optical tagging. CS+ indicates an odorant predicting reward delivery (sucrose). CS− indicates an odorant predicting no sucrose delivery. Adopted from Liu et al. 2014 with permission.

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