Laboratory of Neurodevelopmental Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Department Biozentrum, University of Basel, Basel, Switzerland.
Front Neural Circuits. 2022 May 18;16:911023. doi: 10.3389/fncir.2022.911023. eCollection 2022.
Spontaneous activity generated before the onset of sensory transduction has a key role in wiring developing sensory circuits. From axonal targeting, to synapse formation and elimination, to the balanced integration of neurons into developing circuits, this type of activity is implicated in a variety of cellular processes. However, little is known about its molecular mechanisms of action, especially at the level of genome regulation. Conversely, sensory experience-dependent activity implements well-characterized transcriptional and epigenetic chromatin programs that underlie heterogeneous but specific genomic responses that shape both postnatal circuit development and neuroplasticity in the adult. In this review, we focus on our knowledge of the developmental processes regulated by spontaneous activity and the underlying transcriptional mechanisms. We also review novel findings on how chromatin regulates the specificity and developmental induction of the experience-dependent program, and speculate their relevance for our understanding of how spontaneous activity may act at the genomic level to instruct circuit assembly and prepare developing neurons for sensory-dependent connectivity refinement and processing.
在感觉转导开始之前产生的自发性活动在连接发育中的感觉回路中起着关键作用。从轴突靶向,到突触形成和消除,再到神经元平衡地整合到发育中的回路中,这种类型的活动涉及到各种细胞过程。然而,关于其分子作用机制,特别是在基因组调控水平上的了解甚少。相反,感觉经验依赖性活动实施了特征明确的转录和表观遗传染色质程序,这些程序是形成异质但特定的基因组反应的基础,这些反应塑造了产后回路发育和成年期的神经可塑性。在这篇综述中,我们重点介绍了我们对受自发性活动调节的发育过程以及潜在的转录机制的了解。我们还回顾了关于染色质如何调节经验依赖性程序的特异性和发育诱导的新发现,并推测它们与我们理解自发性活动如何在基因组水平上发挥作用以指导回路组装以及为感觉依赖的连接细化和处理准备发育中的神经元的相关性。