Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
Department of Anatomy and K.K. Leung Brain Research Center, Fourth Military Medical University, Xi'an, China.
Nat Neurosci. 2019 Aug;22(8):1223-1234. doi: 10.1038/s41593-019-0445-9. Epub 2019 Jul 22.
Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.
社交缺陷是自闭症谱系障碍（ASD）的核心临床特征，但潜在的神经机制在很大程度上仍不清楚。我们证明，在 Shank3 基因突变的小鼠的前扣带皮层（ACC）的锥体神经元中，谷氨酸能突触存在结构和功能损伤。在 ACC 中条件性敲除 Shank3 足以产生兴奋性突触功能障碍和社交互动缺陷，而选择性增强 ACC 活性、在 ACC 中恢复 SHANK3 表达或全身给予 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体正变构调节剂可改善 Shank3 突变小鼠的社交行为。我们的发现为 ACC 在调节小鼠社交行为中的作用提供了直接证据，并表明 ACC 功能障碍可能与 ASD 中的社交障碍有关。
