Neuron
Volume 81, Issue 6, 19 March 2014, Pages 1360-1374
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Article
Dorsal Raphe Neurons Signal Reward through 5-HT and Glutamate

https://doi.org/10.1016/j.neuron.2014.02.010Get rights and content
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Highlights

  • Stimulating DRN Pet-1 neurons strongly reinforces behaviors

  • DRN Pet-1 neurons are activated during reward-associated tasks

  • DRN stimulation rapidly shapes neuronal activation patterns in the motor cortex

  • Both 5-HT and glutamate contribute to reward signaling

Summary

The dorsal raphe nucleus (DRN) in the midbrain is a key center for serotonin (5-hydroxytryptamine; 5-HT)-expressing neurons. Serotonergic neurons in the DRN have been theorized to encode punishment by opposing the reward signaling of dopamine neurons. Here, we show that DRN neurons encode reward, but not punishment, through 5-HT and glutamate. Optogenetic stimulation of DRN Pet-1 neurons reinforces mice to explore the stimulation-coupled spatial region, shifts sucrose preference, drives optical self-stimulation, and directs sensory discrimination learning. DRN Pet-1 neurons increase their firing activity during reward tasks, and this activation can be used to rapidly change neuronal activity patterns in the cortex. Although DRN Pet-1 neurons are often associated with 5-HT, they also release glutamate, and both neurotransmitters contribute to reward signaling. These experiments demonstrate the ability of DRN neurons to organize reward behaviors and might provide insights into the underlying mechanisms of learning facilitation and anhedonia treatment.

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These authors contributed equally to this work