Recent evidence has shown that even mild mutations in the Huntingtin gene that are associated with late-onset Huntington’s disease (HD) disrupt various aspects of human neurodevelopment. To determine whether these seemingly subtle early defects affect adult neural function, we investigated neural circuit physiology in newborn HD mice. During the first postnatal week, HD mice have less cortical layer 2/3 excitatory synaptic activity than wild-type mice, express fewer glutamatergic receptors, and show sensorimotor deficits. The circuit self-normalizes in the second postnatal week but the mice nonetheless develop HD. Pharmacologically enhancing glutamatergic transmission during the neonatal period, however, rescues these deficits and preserves sensorimotor function, cognition, and spine and synapse density as well as brain region volume in HD adult mice.

中文翻译：

---

治疗早期产后电路缺陷可延缓小鼠亨廷顿病的发病和病理

最近的证据表明，即使是与迟发性亨廷顿舞蹈病 (HD) 相关的亨廷顿基因的轻微突变也会破坏人类神经发育的各个方面。为了确定这些看似微妙的早期缺陷是否会影响成年神经功能，我们研究了新生 HD 小鼠的神经回路生理学。在出生后的第一周，HD 小鼠的皮质层 2/3 兴奋性突触活动比野生型小鼠少，表达的谷氨酸能受体较少，并表现出感觉运动缺陷。电路在出生后第二周自我正常化，但小鼠仍然会发展为 HD。然而，在新生儿期通过药理学增强谷氨酸能传递可以挽救这些缺陷并保留感觉运动功能、认知、