A Squeak Is Not Enough: Female Presence and Vocal Playback Have Contrasting Effects on c-Fos Expression by Dorsal Raphé Neurons in Lab Mice

The regulation of sensory processing by centralized neuromodulatory systems can alter behavioral responses to social cues. Neuromodulatory systems such as the serotonergic neurons in the dorsal raphé nucleus (DRN) show heterogenous responses to different types of sensory stimuli or to stimulus qualities such as reward, valence, or salience. Sensory neuromodulation could therefore be related to a broader quality of the behavioral context or to specific types of social cues. We assessed this issue by presenting male mice with either playback of female vocal signals associated with defensive aggression (squeaks) or silence, and the presence or absence of a female. Activity in regions of the DRN that project to the auditory midbrain was assessed through co-labeling with antibodies to the serotonin synthetic enzyme tryptophan hydroxylase (TPH) and the immediate early gene product c-Fos. Female presence or absence had the largest effect, decreasing the co-localization of TPH and c-Fos, while the playback of squeaks had effects that were condition-dependent, increasing co-label only when females were absent. Squeak playback further decreased the correlation in the numbers of co-labeled neurons between two dorsal subdivisions of the DRN, the DRD and DRL. These results are inconsistent with an auditory-exclusive feedback loop. Instead, cues associated with female presence heavily influence raphé activity, with squeaks playing a modifying and context-dependent role. Because the elevation of serotonin in the IC causes males to become more responsive to female squeaks, these findings suggest that a nuanced interaction of positive and negative cues during social interaction may fine-tune male responses to the vocalization of social partners, in part through the serotonergic system.