Study On The Activity Of Different Types Of Neurons In Rear Rear Nucleus In Reward Related Behavior

Primary rewards such as food and sex are critical for the survival and reproduction of animal species. The dorsal raphe nucleus (DRN) participates in organizing a broad spectrum of reward-related behaviors. It represents the primary source of forebrain serotonin (5-HT), but also contains neurons that release other neurotransmitters, such as GAB A. It remains unclear how genetically defined neurons in the DRN respond to various primary rewards in freely behaving animals. Moreover, DRN is proposed to be involved in regulating behavioral states, but it remains unknown yet how the activity patterns of different neuron types correspond to behavioral states when an animal is seeking rewards. Here we addressed these questions using cell type-specific fiber photometry and single-unit recording from 5-HT neurons and GABA neurons from the DRN of freely behaving mice.Our recordings show that consuming primary rewards including sucrose, food, sex, and social interaction rapidly activates DRN 5-HT neurons but inhibits GABA neurons. Surprising delivery of sucrose solution directly into the oral cavity also significantly increases the activity of 5-HT neurons, but aversive stimuli including quinine and footshock cannot. By contrast, aversive footshocks activate DRN GABA neurons.We also demonstrate that DRN neurons show activity changes associated with the behavioral states. In a sucrose foraging task, animals were trained to wait in the reward zone for delayed reward delivery and switched to search mode by going back to a different zone to initiate sucrose search, suggesting the change of behavioral states between exploitation and exploration. DRN 5-HT neurons show higher activity during the exploitation state and lower activity during the exploration state. Specifically, the exploitation state includes reward expectation and reward consumption phase. Typical 5-HT neurons fire tonically during reward expectation and phasically upon reward acquisition. By contrast, DRN GABA neurons exhibit lower activity during the exploitation state and higher activity during the exploration state. Finally, dopamine (DA) neurons in the ventral tegmental area (VTA) do not show significant correlation with animals’ exploration/exploitation behavioral state. These DA neurons fire phasically upon reward acquisition but show no significant activation during reward expectation.In summary, our experiments reveal that DRN 5-HT neurons respond to general reward signals during both the anticipatory and the consummatory phases, whereas GABA neurons exhibit an overall opposite activity patterns. Moreover, our data support the hypothesis that the activity of 5-HT neurons promotes exploitation and suppresses exploration. Finally,5-HT neurons and dopamine neurons may play different roles in reward processing. Our findings identify DRN 5-HT neurons as a key player in organizing reward-related behaviors and have multiple implications in reward theory and the etiology of psychiatric disorders associated with altered 5-HT signaling.