Abstract：
Synapses change their weights in response to neuronal activity and in turn, neuronal networks alter their response properties and ultimately allow the brain to store information as memories. As for memories, not all events are maintained over time. Maintenance of synaptic plasticity depends on the interplay between functional changes at synapses and the synthesis of plasticity-related proteins that are involved in stabilizing the initial functional changes. Different forms of synaptic plasticity coexist in time and across the neuronal dendritic area. Thus, homosynaptic plasticity refers to activity-dependent synaptic modifications that are input-specific, whereas heterosynaptic plasticity relates to changes in non-activated synapses. Heterosynaptic forms of plasticity, such as synaptic cooperation and competition allow neurons to integrate events that occur separated by relatively large time windows, up to one hour. Here, we show that activation of Cdc42, a Rho GTPase that regulates actin cytoskeleton dynamics, is necessary for the maintenance of long-term potentiation (LTP) in a time-dependent manner. Inhibiting Cdc42 activation does not alter the time-course of LTP induction and its initial expression but blocks its late maintenance. We show that Cdc42 activation is involved in the phosphorylation of cofilin, a protein involved in modulating actin filaments and that weak and strong synaptic activation leads to similar levels on cofilin phosphorylation, despite different levels of LTP expression. We show that Cdc42 activation is required for synapses to interact by cooperation or competition, supporting the hypothesis that modulation of the actin cytoskeleton provides an activity-dependent and time-restricted permissive state of synapses allowing synaptic plasticity to occur. We found that under competition, the sequence in which synapses are activated determines the degree of LTP destabilization, demonstrating that competition is an active destabilization process. Taken together, we show that modulation of actin cytoskeleton by Cdc42 activation is necessary for the expression of homosynaptic and heterosynaptic forms of plasticity. Determining the temporal and spatial rules that determine whether synapses cooperate or compete will allow us to understand how memories are associated.
摘要：
突触响应神经元活动而改变其权重，神经元网络改变其响应特性，并最终允许大脑将信息存储为记忆。至于回忆,并非所有事件都随时间保持。突触可塑性的维持取决于突触的功能变化与可塑性相关蛋白的合成之间的相互作用，这些蛋白与稳定初始功能变化有关。不同形式的突触可塑性在时间上和整个神经元树突区域共存。因此，同突触可塑性是指活动依赖的突触修饰，是输入特异性的，而异质突触可塑性与非激活突触的变化有关。可塑性的异质突触形式，例如突触合作和竞争允许神经元整合由相对较大的时间窗口分开发生的事件，最多1小时。在这里，我们显示Cdc42，一种调节肌动蛋白细胞骨架动力学的RhoGTP酶的激活，对于以时间依赖性方式维持长期增强（LTP）是必需的。抑制Cdc42活化不会改变LTP诱导及其初始表达的时间过程，但会阻止其后期维持。我们证明Cdc42的激活参与了cofilin的磷酸化，一种参与调节肌动蛋白丝的蛋白质，弱和强的突触激活导致类似的cofilin磷酸化水平，尽管LTP表达水平不同。我们表明，Cdc42激活是突触通过合作或竞争相互作用所必需的，支持以下假设：肌动蛋白细胞骨架的调节提供了突触的活动依赖性和时间限制的允许状态，从而允许突触可塑性发生。我们发现在竞争下,突触激活的顺序决定了LTP不稳定的程度，证明竞争是一个积极的破坏稳定的过程。一起来看,我们表明，通过Cdc42激活调节肌动蛋白细胞骨架是表达可塑性的同质突触和异质突触形式所必需的。确定确定突触是合作还是竞争的时间和空间规则将使我们能够理解记忆是如何关联的。
