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Neurobiol Learn Mem. 2016 Nov;135:40-49. doi: 10.1016/j.nlm.2016.08.008. Epub 2016 Aug 18.

Do dorsal raphe 5-HT neurons encode "beneficialness"?

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National Institute of Biological Sciences, Beijing 102206, China; School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:
National Institute of Biological Sciences, Beijing 102206, China; Graduate School of Peking Union Medical College, Beijing 100730, China.
National Institute of Biological Sciences, Beijing 102206, China.


The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) affects numerous behavioral and physiological processes. Drugs that alter 5-HT signaling treat several major psychiatric disorders and may lead to widespread abuse. The dorsal raphe nucleus (DRN) in the midbrain provides a majority of 5-HT for the forebrain. The importance of 5-HT signaling propels the search for a general theoretical framework under which the diverse functions of the DRN 5-HT neurons can be interpreted and additional therapeutic solutions may be developed. However, experimental data so far support several seeming irreconcilable theories, suggesting that 5-HT neurons mediate behavioral inhibition, aversive processing, or reward signaling. Here, we review recent progresses and propose that DRN 5-HT neurons encode "beneficialness" - how beneficial the current environmental context represents for an individual. Specifically, we speculate that the activity of these neurons reflects the possible net benefit of the current context as determined by p·R-C, in which p indicates reward probability, R the reward value, and C the cost. Through the widespread projections of these neurons to the forebrain, the beneficialness signal may reconfigure neural circuits to bias perception, boost positive emotions, and switch behavioral choices. The "beneficialness" hypothesis can explain many conflicting observations, and at the same time raises new questions. We suggest additional experiments that will help elucidate the exact computational functions of the DRN 5-HT neurons.


Anhedonia; Cost; Decision-making; Depression; Dopamine; Emotion; Feeding behavior; Learning and memory; Pleasure; Punishment; Reward; Serotonin; Social behavior

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