UPMC Univ Paris 6 and CNRS, UMR 7102 Neurobiologie des Processus Adaptatifs, Paris, France.
Cerebellum. 2013 Jun;12(3):319-21. doi: 10.1007/s12311-012-0443-x.
The assembly of neural circuits involves multiple sequential steps, in particular the formation and maturation of synaptic connections. This often prolonged process involves several stages including the appropriate morphological and physiological maturation of each synaptic partner as well as their mutual interaction in order to ensure correct cellular and subcellular targeting. Understanding the processes involved becomes critical if neural circuits are to be appropriately reassembled following lesion, atrophy or neurodegeneration. We study the climbing fibre to Purkinje cell synapse as an example of a neural circuit which undergoes initial synaptic formation, selective stabilisation and elimination of redundant connections, in order to better understand the relative roles of each synaptic partner in the process of synaptogenesis and post-lesion synapse reformation. In particular, we are interested in the molecules which may underlie these processes. Here, we present data showing that the maturational state of both the target Purkinje cell and the climbing fibre axon influence their capacity for synapse formation. The climbing fibre retains some ability to recapitulate developmental processes irrespective of its maturational state. In contrast, the experience of synaptic formation and selective stabilisation/elimination permanently changes the Purkinje cell so that it cannot be repeated. Thus, if the climbing fibre-Purkinje cell synapse is recreated after the period of normal maturation, the process of synaptic competition, involving the gradual weakening of one climbing fibre synapse and stabilisation of another, no longer takes place. Moreover, we show that these processes of synaptic competition can only proceed during a specific developmental phase. To understand why these changes occur, we have investigated the role of molecules involved in the development of the olivocerebellar path and show that brain-derived neurotrophic factor, through activation of its receptor TrkB, as well as polysialated neural cell adhesion molecule and the transcription factor RORα regulate these processes.
神经回路的组装涉及多个连续的步骤，特别是突触连接的形成和成熟。这个过程通常很漫长，涉及多个阶段，包括每个突触伙伴的适当形态和生理成熟，以及它们相互作用以确保正确的细胞和亚细胞靶向。如果要在损伤、萎缩或神经退行性变后适当重新组装神经回路，了解所涉及的过程就变得至关重要。我们以 climbing fibre 到 Purkinje 细胞突触为例，研究一个经历初始突触形成、选择性稳定和冗余连接消除的神经回路，以更好地理解每个突触伙伴在突触发生和损伤后突触重构过程中的相对作用。特别是，我们对可能构成这些过程的分子感兴趣。在这里，我们提供的数据表明，靶 Purkinje 细胞和 climbing fibre 轴突的成熟状态都影响它们形成突触的能力。climbing fibre 保留了一些在其成熟状态下重新进行发育过程的能力。相比之下，经历突触形成和选择性稳定/消除会永久改变 Purkinje 细胞，使其无法重复。因此，如果在正常成熟后重新创建 climbing fibre-Purkinje 细胞突触，涉及一个 climbing fibre 突触逐渐减弱和另一个稳定的突触的竞争过程将不再发生。此外，我们表明，这些突触竞争过程只能在特定的发育阶段进行。为了了解为什么会发生这些变化，我们研究了参与橄榄小脑通路发育的分子的作用，并表明脑源性神经营养因子通过其受体 TrkB 的激活，以及多涎酸神经细胞黏附分子和转录因子 RORα 调节这些过程。
