Juvenile social isolation reduces sociability in adulthood, but the underlying neural circuit mechanisms are poorly understood. We found that, in male mice, 2 weeks of social isolation immediately following weaning leads to a failure to activate medial prefrontal cortex neurons projecting to the posterior paraventricular thalamus (mPFC→pPVT) during social exposure in adulthood. Chemogenetic or optogenetic suppression of mPFC→pPVT activity in adulthood was sufficient to induce sociability deficits without affecting anxiety-related behaviors or preference toward rewarding food. Juvenile isolation led to both reduced excitability of mPFC→pPVT neurons and increased inhibitory input drive from low-threshold-spiking somatostatin interneurons in adulthood, suggesting a circuit mechanism underlying sociability deficits. Chemogenetic or optogenetic stimulation of mPFC→pPVT neurons in adulthood could rescue the sociability deficits caused by juvenile isolation. Our study identifies a pair of specific medial prefrontal cortex excitatory and inhibitory neuron populations required for sociability that are profoundly affected by juvenile social experience.

青少年的社会隔离降低了成年后的社交能力，但对潜在的神经回路机制了解甚少。我们发现，在雄性小鼠中，断奶后2周的社交隔离会导致成年社交暴露期间无法激活投射到后室旁丘脑（mPFC→pPVT）的内侧前额叶皮层神经元。成年期对mPFC→pPVT活性的化学或光遗传抑制足以诱发社交缺陷，而不影响焦虑相关行为或对奖励食物的偏爱。少年隔离既导致mPFC→pPVT神经元的兴奋性降低，也导致成年期低阈值生长抑素中间神经元的抑制性输入驱动增加，表明存在社交能力缺陷的电路机制。成年期mPFC→pPVT神经元的化学遗传或光遗传刺激可以挽救青少年隔离引起的社交能力缺陷。我们的研究确定了社交活动所需的一对特定的内侧前额叶皮层兴奋性和抑制性神经元群体，这些群体深受少年社会经历的影响。