Abstract:
In vivo optical imaging is a powerful tool for revealing brain structure and function at both the circuit and cellular levels. Here, we provide a systematic review of findings obtained from in vivo imaging studies of mouse models of neurodevelopmental disorders, including the monogenic disorders fragile X syndrome, Rett syndrome, and Angelman syndrome, which are caused by genetic abnormalities of FMR1, MECP2, and UBE3A, as well as disorders caused by copy number variations (15q11-13 duplication and 22q11.2 deletion) and BTBR mice as an inbred strain model of autism spectrum disorder (ASD). Most studies visualize the structural and functional responsiveness of cerebral cortical neurons to sensory stimuli and the developmental and experience-dependent changes in these responses as a model of brain functions affected by these disorders. The optical imaging techniques include two-photon microscopy of fluorescently labeled dendritic spines or neurons loaded with fluorescent calcium indicators and macroscopic imaging of cortical activity using calcium indicators, voltage-sensitive dyes or intrinsic optical signals. Studies have revealed alterations in the density, stability, and turnover of dendritic spines, aberrant cortical sensory responses, impaired inhibitory function, and concomitant failure of circuit maturation as common causes for neurological deficits. Mechanistic hypotheses derived from in vivo imaging also provide new directions for therapeutic interventions. For instance, it was recently demonstrated that early postnatal administration of a selective serotonin reuptake inhibitor (SSRI) restores impaired cortical inhibitory function and ameliorates the aberrant social behaviors in a mouse model of ASD. We discuss the potential use of SSRIs for treating ASDs in light of these findings.
摘要:
体内光学成像是在电路和细胞水平上揭示大脑结构和功能的强大工具。这里,我们对神经发育障碍小鼠模型的体内成像研究结果进行了系统综述,包括单基因疾病脆性X综合征,Rett综合征,和Angelman综合征,它们是由FMR1、MECP2和UBE3A的遗传异常引起的,以及由拷贝数变异(15q11-13重复和22q11.2缺失)和BTBR小鼠作为自闭症谱系障碍(ASD)的近交系模型引起的疾病。大多数研究将大脑皮层神经元对感觉刺激的结构和功能反应以及这些反应的发育和经验依赖性变化可视化为受这些疾病影响的脑功能模型。光学成像技术包括双光子显微镜的荧光标记的树突棘或装载有荧光钙指标的神经元和使用钙指标的皮质活动的宏观成像,电压敏感染料或固有光信号。研究表明密度发生了变化,稳定性,和树突棘的周转,异常的皮层感觉反应,抑制功能受损,以及伴随的回路成熟失败是神经系统缺陷的常见原因。来自体内成像的机制假设也为治疗干预提供了新的方向。例如,最近证明,在ASD小鼠模型中,出生后早期给予选择性5-羟色胺再摄取抑制剂(SSRI)可恢复受损的皮质抑制功能并改善异常的社会行为。根据这些发现,我们讨论了SSRIs治疗ASDs的潜在用途。