Department of Basic Neuroscience, University of Geneva, Geneva, Switzerland.
Laboratory of Child Growth and Development, University of Geneva, Geneva, Switzerland.
Elife. 2022 Apr 22;11:e73421. doi: 10.7554/eLife.73421.
Social interaction during adolescence strongly influences brain function and behavior, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidence has shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference. Behavioral changes were accompanied by the acute hyperexcitability of putative dopamine (pDA) neurons in the ventral tegmental area and long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex. Social isolation-dependent behavioral deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus of the hypothalamus. These results demonstrate that social isolation in male mice has acute and long-lasting effects on social interaction and suggest that homeostatic adaptations mediate these effects within the reward circuit.
青春期的社会互动强烈影响大脑功能和行为，最近的大流行强调了社交隔离对心理健康的毁灭性影响。虽然越来越多的证据表明奖励系统在编码社会互动的特定方面的重要性，但社交隔离对奖励系统和成年后社交技能发展的影响在很大程度上仍不清楚。在这里，我们发现青春期雄性小鼠 1 周的社交隔离会增加社交互动，而牺牲社交习惯化和社交新颖性偏好。行为变化伴随着腹侧被盖区中假定多巴胺（pDA）神经元的急性超兴奋性，以及投射到前额叶皮层的 pDA 神经元上兴奋性输入处的 GluA2 缺失 AMPAR 的持久表达。通过下丘脑室旁核催产素神经元的化学遗传抑制，可逆转社交隔离依赖性的行为缺陷以及神经活动和突触可塑性的变化。这些结果表明，雄性小鼠的社交隔离对社交互动有急性和持久的影响，并表明在奖励回路中，内稳态适应介导了这些影响。
