Neural activity and theta rhythmicity in the anterior hypothalamic nucleus are involved in regulating social investigation

Social interactions are highly complex, involving both approach and avoidance actions towards specific individuals, dependent on the social context. Currently, the brain regions subserving these behaviors are not fully known. The anterior hypothalamic nucleus (AHN) is a relatively unstudied and poorly defined brain area, known as part of the medial hypothalamic defensive system. Recent studies that examined the role of the AHN in various contexts have yielded contradicting results regarding its contribution to approach, avoidance, and escape behaviors. Yet, none of these studies has directly examined its role in social interactions. Here we explored the role of AHN neurons in regulating approach and avoidance actions towards distinct stimuli during various types of social interactions, using electrophysiological recording of neural activity in the AHN of behaving mice, c-Fos staining, and direct optogenetic stimulation. We found that theta rhythmicity in the AHN was enhanced during affiliative interactions, but decreased during aversive ones. Moreover, spiking activity of AHN neurons was found to be elevated more persistently during investigation of social stimuli, as compared to objects. Notably, AHN neuronal firing was found to be modulated by theta rhythmicity during social interactions. Finally, we found that during social interaction, direct optogenetic stimulation of AHN neurons augmented approach behavior towards stimuli associated with the optogenetic activation. Overall, our results suggest a context-dependent role for AHN neuronal activity in regulating approach behavior during social interactions, and for theta rhythmicity in mediating the valence of the social context.