Single-cell activity and network properties of dorsal raphe serotonin neurons during emotional behaviors

The mammalian serotonin system modulates a wide variety of emotional behaviors and states, including reward processing, anxiety, and social interaction. To reveal the underlying patterns of neural activity, we visualized serotonergic neurons in the dorsal raphe nucleus (DRN5-HT) of mice using miniaturized microscopy and calcium imaging during diverse emotional behaviors. In total, we imaged the activity of over 2,000 genetically-identified serotonin neurons. We discovered discrete ensembles of cells with highly correlated activity and found that DRN5-HT neurons are preferentially recruited by emotionally salient stimuli as opposed to neutral stimuli. Individual DRN5-HT neurons responded to diverse combinations of salient stimuli, with some preference for valence and sensory modality. Anatomically-defined subpopulations projecting to either a reward-related structure, the ventral tegmental area, or an anxiety-related structure, the bed nucleus of the stria terminalis, contained all response types, but were enriched in reward- and anxiety-responsive cells, respectively. Our results suggest that the DRN serotonin system responds to emotional salience using correlated ensembles with mixed selectivity and biases in downstream connectivity.