Flores Juan C, Sarkar Dipannita, Zito Karen
Center for Neuroscience, University of California, Davis, CA 95618.
Proc Natl Acad Sci U S A. 2025 Jan 14;122(2):e2410433122. doi: 10.1073/pnas.2410433122. Epub 2025 Jan 7.
How newly formed memories are preserved while brain plasticity is ongoing has been a source of debate. One idea is that synapses which experienced recent plasticity become resistant to further plasticity, a type of metaplasticity often referred to as saturation. Here, we probe the local dendritic mechanisms that limit plasticity at recently potentiated synapses. We show that recently potentiated individual synapses exhibit a synapse-specific refractory period for further potentiation. We further found that the refractory period is associated with reduced postsynaptic CaMKII signaling; however, stronger synaptic activation fully restored CaMKII signaling but only partially restored the ability for further plasticity. Importantly, the refractory period is released after one hour, a timing that coincides with the enrichment of several postsynaptic proteins to preplasticity levels. Notably, increasing the level of the postsynaptic scaffolding protein, PSD95, but not of PSD93, overcomes the refractory period. Our results support a model in which potentiation at a single synapse is sufficient to initiate a synapse-specific refractory period that persists until key postsynaptic proteins regain their steady-state synaptic levels.
在大脑可塑性持续进行的过程中，新形成的记忆是如何保存的一直是一个争论的焦点。一种观点认为，经历了近期可塑性变化的突触会对进一步的可塑性变化产生抗性，这种元可塑性通常被称为饱和。在这里，我们探究了限制近期增强突触可塑性的局部树突机制。我们发现，近期增强的单个突触对进一步增强表现出突触特异性不应期。我们进一步发现，不应期与突触后CaMKII信号传导减少有关；然而，更强的突触激活完全恢复了CaMKII信号传导，但仅部分恢复了进一步可塑性的能力。重要的是，不应期在一小时后解除，这一时刻与几种突触后蛋白富集到可塑性变化前水平相吻合。值得注意的是，增加突触后支架蛋白PSD95的水平，而不是PSD93的水平，可克服不应期。我们的结果支持这样一种模型，即单个突触的增强足以启动一个突触特异性不应期，该不应期会持续到关键突触后蛋白恢复其稳态突触水平。
