Skirball Institute, Department of Neuroscience and Physiology, Department of Anesthesiology, New York University School of Medicine, New York, NY 10016.
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Proc Natl Acad Sci U S A. 2021 Dec 14;118(50). doi: 10.1073/pnas.2114856118.
Changes in synaptic connections are believed to underlie long-term memory storage. Previous studies have suggested that sleep is important for synapse formation after learning, but how sleep is involved in the process of synapse formation remains unclear. To address this question, we used transcranial two-photon microscopy to investigate the effect of postlearning sleep on the location of newly formed dendritic filopodia and spines of layer 5 pyramidal neurons in the primary motor cortex of adolescent mice. We found that newly formed filopodia and spines were partially clustered with existing spines along individual dendritic segments 24 h after motor training. Notably, posttraining sleep was critical for promoting the formation of dendritic filopodia and spines clustered with existing spines within 8 h. A fraction of these filopodia was converted into new spines and contributed to clustered spine formation 24 h after motor training. This sleep-dependent spine formation via filopodia was different from retraining-induced new spine formation, which emerged from dendritic shafts without prior presence of filopodia. Furthermore, sleep-dependent new filopodia and spines tended to be formed away from existing spines that were active at the time of motor training. Taken together, these findings reveal a role of postlearning sleep in regulating the number and location of new synapses via promoting filopodial formation.
突触连接的变化被认为是长时记忆存储的基础。先前的研究表明，睡眠对于学习后突触形成很重要，但睡眠如何参与突触形成过程尚不清楚。为了解决这个问题，我们使用颅外双光子显微镜来研究学习后睡眠对青春期小鼠初级运动皮层第 5 层锥体神经元新形成的树突丝状伪足和棘突位置的影响。我们发现，在运动训练后 24 小时，新形成的丝状伪足和棘突部分与现有棘突沿着单个树突段聚类。值得注意的是，训练后睡眠对于在 8 小时内促进与现有棘突聚类的树突丝状伪足和棘突的形成至关重要。这些丝状伪足中的一部分转化为新的棘突，并有助于运动训练后 24 小时的聚类棘突形成。这种通过丝状伪足的睡眠依赖性棘突形成不同于再训练诱导的新棘突形成，后者从没有丝状伪足存在的树突干中出现。此外，睡眠依赖性新丝状伪足和棘突往往远离在运动训练时活跃的现有棘突形成。总之，这些发现揭示了学习后睡眠通过促进丝状伪足形成来调节新突触的数量和位置的作用。
