Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKC5 during Plasticity
Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKC5 during Plasticity
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DOI：
10.1523/jneurosci.0208-22.2023
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发表时间：
2023-07-26
影响因子：
5.3
通讯作者：
Yasuda, Ryohei
中科院分区：
文献类型：
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作者：
Colgan, Lesley A.;Parra-Bueno, Paula;Yasuda, Ryohei
突触的活动依赖性可塑性被认为是学习的细胞基础。这些突触变化是通过协调突触中的局部生化反应和细胞核中基因转录的变化来调节神经元回路和行为的。蛋白激酶C（PKC）家族的同工酶早已被确立为突触可塑性的关键。然而，由于缺乏合适的同工酶特异性工具，PKC同工酶的新亚家族的作用在很大程度上是未知的。在这里，通过荧光寿命成像-荧光共振能量转移活性传感器的发展，我们研究了新的PKC同工酶在突触可塑性的CA 1锥体神经元的小鼠的任何性别。我们发现PKC 5在TrkB和DAG产生的下游被激活，并且其激活的时空性质取决于可塑性刺激。响应于单棘可塑性，PKC 5主要在受刺激的棘中被激活，并且是可塑性的局部表达所需的。然而，在响应多棘刺激时，PKC 5的持久和扩散激活与刺激的棘的数量成比例，并通过调节cAMP反应元件结合蛋白的活性，将棘可塑性与细胞核中的转录结合起来。因此，PKC 5在促进突触可塑性方面发挥双重功能作用。
The activity-dependent plasticity of synapses is believed to be the cellular basis of learning. These synaptic changes are medi- ated through the coordination of local biochemical reactions in synapses and changes in gene transcription in the nucleus to modulate neuronal circuits and behavior. The protein kinase C (PKC) family of isozymes has long been established as critical for synaptic plasticity. However, because of a lack of suitable isozyme-specific tools, the role of the novel subfamily of PKC isozymes is largely unknown. Here, through the development of fluorescence lifetime imaging-fluorescence resonance energy transfer activity sensors, we investigate novel PKC isozymes in synaptic plasticity in CA1 pyramidal neurons of mice of either sex. We find that PKC5 is activated downstream of TrkB and DAG production, and that the spatiotemporal nature of its acti- vation depends on the plasticity stimulation. In response to single-spine plasticity, PKC5 is activated primarily in the stimu- lated spine and is required for local expression of plasticity. However, in response to multispine stimulation, a long-lasting and spreading activation of PKC5 scales with the number of spines stimulated and, by regulating cAMP response-element binding protein activity, couples spine plasticity to transcription in the nucleus. Thus, PKC5 plays a dual functional role in facilitating synaptic plasticity.