Serotonin neurons in the dorsal raphe nucleus encode reward signals

Li, Yang; Zhong, Weixin; Wang, Daqing; Feng, Qiru; Liu, Zhixiang; Zhou, Jingfeng; Jia, Chunying; Hu, Fei; Zeng, Jiawei; Guo, Qingchun; Fu, Ling; Luo, Minmin

doi:10.1038/ncomms10503

Cited by 311 publications

(351 citation statements)

References 69 publications

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“…We first tested this hypothesis by using the calcium reporter GCaMP6f (22) to directly measure neural Ca 2+ signals by fiber photometry after changes in environmental temperature. Similar experimental setups have yielded stable recordings from the dorsal raphe (23) (Fig. 3A).…”

Section: Resultsmentioning

confidence: 76%

A hypothalamic circuit that controls body temperature

Zhao

Yang

Gao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

236

254

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The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify neurons that are activated by a thermal challenge and found induced expression in subsets of neurons within the ventral part of the lateral preoptic nucleus (vLPO) and the dorsal part of the dorsomedial hypothalamus (DMD). Activation of GABAergic neurons in the vLPO using optogenetics reduced body temperature, along with a decrease in physical activity. Optogenetic inhibition of these neurons resulted in fever-level hyperthermia. These GABAergic neurons project from the vLPO to the DMD and optogenetic stimulation of the nerve terminals in the DMD also reduced body temperature and activity. Electrophysiological recording revealed that the vLPO GABAergic neurons suppressed neural activity in DMD neurons, and fiber photometry of calcium transients revealed that DMD neurons were activated by cold. Accordingly, activation of DMD neurons using designer receptors exclusively activated by designer drugs (DREADDs) or optogenetics increased body temperature with a strong increase in energy expenditure and activity. Finally, optogenetic inhibition of DMD neurons triggered hypothermia, similar to stimulation of the GABAergic neurons in the vLPO. Thus, vLPO GABAergic neurons suppressed the thermogenic effect of DMD neurons. In aggregate, our data identify vLPO→DMD neural pathways that reduce core temperature in response to a thermal challenge, and we show that outputs from the DMD can induce activity-induced thermogenesis.

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Section: Resultsmentioning

confidence: 76%

A hypothalamic circuit that controls body temperature

Zhao

Yang

Gao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

236

254

View full text Add to dashboard Cite

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“…5-HT has been shown to be related to feelings of well-being and happiness Li et al, 2016). The primary sources of 5-HT release are the raphe nucleus in the brain and the gastrointestinal tract (Ben Arous et al, 2009).…”

Section: -Hydroxytryptamine Synthesized In the Aorta-gonadmesonephromentioning

confidence: 99%

5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival

Wang

Liu

2017

Mechanisms of Development

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“…Wagner et al [57] suggested that the cerebellar granule cells may encode the expectation of reward. Luo et al [58], Li et al [59], and Hayashi et al [60] found that serotonin neurons in the dorsal raphe nucleus can encode reward signals. Some physiological and theoretical works [17,18,[61][62][63] focus on D1 and D2 receptors in the ventral striatum and suggested that they play an important role in computing reward-prediction error.…”

Section: Complexitymentioning

confidence: 99%

Parallel Excitatory and Inhibitory Neural Circuit Pathways Underlie Reward-Based Phasic Neural Responses

2018

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Phasic activity of dopaminergic (DA) neurons in the ventral tegmental area or substantia nigra compacta (VTA/SNc) has been suggested to encode reward-prediction error signal for reinforcement learning. Recent studies have shown that the lateral habenula (LHb) neurons exhibit a similar response, but for nonrewarding or punishment signals. Hence, the transient signaling role of LHb neurons is opposite that of DA neurons and also that of several other brain nuclei such as the border region of the globus pallidus internal segment (GPb) and the rostral medial tegmentum (RMTg). Previous theoretical models have investigated the neural circuit mechanism underlying reward-based phasic activity of DA neurons, but the feasibility of a larger neural circuit model to account for the observed reward-based phasic activity in other brain nuclei such as the LHb has yet to be shown. Here, we propose a largescale neural circuit model and show that parallel excitatory and inhibitory pathways underlie the learned neural responses across multiple brain regions. Specifically, the model can account for the phasic neural activity observed in the GPb, LHb, RMTg, and VTA/SNc. Based on sensitivity analysis, the model is found to be robust against changes in the overall neural connectivity strength. The model also predicts that striosomes play a key role in the phasic activity of VTA/SNc and LHb neurons by encoding previous and expected rewards. Taken together, our model identifies the important role of parallel neural circuit pathways in accounting for phasic activity across multiple brain areas during reward and punishment processing.

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Serotonin neurons in the dorsal raphe nucleus encode reward signals

Cited by 311 publications

References 69 publications

A hypothalamic circuit that controls body temperature

A hypothalamic circuit that controls body temperature

5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival

Parallel Excitatory and Inhibitory Neural Circuit Pathways Underlie Reward-Based Phasic Neural Responses

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