Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Cell Rep. 2023 Jul 25;42(7):112815. doi: 10.1016/j.celrep.2023.112815. Epub 2023 Jul 18.
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 activity 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 neurons 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.
下丘脑通过编码内部状态在调节社会行为方面起着至关重要的作用。下丘脑食欲肽/下丘脑泌素神经元最初被确定为睡眠和食欲的调节剂，对于情绪和动机行为很重要。然而，它们在社会行为中的作用尚不清楚。使用光纤光度法和行为分析，我们在这里表明，食欲肽神经元根据社会交往的性质差异编码社会歧视。食欲肽神经元活性的光遗传学抑制或 hcrt-1 受体阻断会减少雄性小鼠参与社会互动的时间，但不会减少雌性小鼠参与社会互动的时间。在社会互动过程中减少 hcrt-1 受体信号会导致雄性的岛叶皮层和腹侧被盖区活动改变。我们的数据表明，食欲肽神经元作为社会网络中性别二态性调节剂，对治疗具有社会功能障碍的神经精神疾病具有重要意义，特别是考虑到性别之间的发病率差异。
