Hypocretin/orexin neurons encode social discrimination and exhibit a sex-dependent for social interaction

The hypothalamus plays a crucial role in the modulation of social behavior by encoding internal states. The hypothalamic hypocretin/orexin neurons, initially identified as regulators of sleep and appetite, are important for emotional and motivated behaviors. However, their role in social behavior remains unclear. Using fiber photometry and behavioral analysis, we show here that hypocretin neurons differentially encode social discrimination based on the nature of social encounters. The optogenetic inhibition of hypocretin neuron ac-tivity or blocking of hcrt-1 receptors reduces the amount of time mice are engaged in social interaction in males but not in females. Reduced hcrt-1 receptor signaling during social interaction is associated with altered activity in the insular cortex and ventral tegmental area in males. Our data implicating hypocretin neu-rons as sexually dimorphic regulators within social networks have significant implications for the treatment of neuropsychiatric diseases with social dysfunction, particularly considering varying prevalence among sexes.

Automated summary

The hypothalamus is crucial in regulating social behavior by encoding internal states. Hypocretin/orexin neurons in the hypothalamus, initially known for their role in sleep and appetite regulation, also play a key role in emotional and motivated behaviors. However, their involvement in social behavior is still not well understood.