神经回路的经验依赖性和自主性的改变被认为是自闭症谱系障碍(ASD)的基础,尽管尚不清楚是什么突触特征负责。这里,利用丙戊酸诱导的ASD模型,与特发性ASD有共同的分子特征,我们通过双光子显微镜研究了背侧前额叶皮层上层锥体神经元和相邻轴突的簇状树突的结构动力学变化。在Marmosets模型中,树突脊柱周转上调,棘刺成簇产生,并且比对照and猴存活的频率更高。局部轴突的突触前束,但不是在连合远程轴突中,展示了模型猕猴桃中的超动态周转,提示投影特异性可塑性的改变。有趣的是,经鼻给予催产素可减弱模型绒猴中聚集的脊柱出现。增强的群集脊柱生成,可能是某些突触前伴侣独有的,可能与ASD相关,是一个潜在的治疗靶点。
Alterations in the experience-dependent and autonomous elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD), though it is unclear what synaptic traits are responsible. Here, utilizing a valproic acid-induced ASD marmoset model, which shares common molecular features with idiopathic ASD, we investigate changes in the structural dynamics of tuft dendrites of upper-layer pyramidal neurons and adjacent axons in the dorsomedial prefrontal cortex through two-photon microscopy. In model marmosets, dendritic spine turnover is upregulated, and spines are generated in clusters and survived more often than in control marmosets. Presynaptic boutons in local axons, but not in commissural long-range axons, demonstrate hyperdynamic turnover in model marmosets, suggesting alterations in projection-specific plasticity. Intriguingly, nasal oxytocin administration attenuates clustered spine emergence in model marmosets. Enhanced clustered spine generation, possibly unique to certain presynaptic partners, may be associated with ASD and be a potential therapeutic target.