Shim Hyun Geun, Jang Dong Cheol, Lee Jaegeon, Chung Geehoon, Lee Sukchan, Kim Yong Gyu, Jeon Da Eun, Kim Sang Jeong
Department of Physiology and.
Department of Biomedical Science, Seoul National University College of Medicine, 03087 Seoul, Korea.
J Neurosci. 2017 Jun 7;37(23):5659-5669. doi: 10.1523/JNEUROSCI.3464-16.2017. Epub 2017 May 11.
Long-term depression (LTD) at the parallel fiber (PF)-to-cerebellar Purkinje cell (PC) synapse is implicated in the output of PCs, the sole output of the cerebellar cortex. In addition to synaptic plasticity, intrinsic excitability is also one of the components that determines PC output. Although long-term potentiation of intrinsic excitability (LTP-IE) has been suggested, it has yet to be investigated how PF-PC LTD modifies intrinsic excitability of PCs. Here, we show that pairing of the PF and climbing fiber (CF) for PF-PC LTD induction evokes LTD-IE in cerebellar PCs from male C57BL/6 mice. Interestingly, this intrinsic plasticity showed different kinetics from synaptic plasticity, but both forms of plasticity share Ca signaling and protein kinase C pathway as their underlying mechanism. Although small-conductance Ca-activated K channels play important roles in LTP-IE, no direct implication has been found. After PF-PC LTD induction, neither the temporal summation of dendritic EPSP nor the power of spike frequency adaptation is changed, indicating that cerebellar LTD executes the information processing in a quantitative way without quality changes of synaptic integration and generation of output signals. Our results suggest that LTD-IE may have a synergistic effect with synaptic depression on the total net output of neurons by amplifying the modification of PF synaptic transmission. Although the output of Purkinje cells (PCs) is a critical component of cerebellum-dependent learning and memory, the changes of PC excitability when synaptic LTD occurs are unclear. Here, we show that the induction of PF-PC LTD evokes LTD-IE in PCs. Our observation complements previous intrinsic plasticity phenomenon of long-term potentiation of intrinsic excitability (LTP-IE), providing evidence for the idea that intrinsic plasticity has bidirectionality as synaptic plasticity. LTD-IE occurs together with synaptic LTD and both phenomena are dependent on the Ca signaling pathway. Furthermore, our findings raise the prospect that this synaptic and intrinsic plasticity acts synergistically in PCs to modify neuronal activity in the same direction when learning occurs.
平行纤维（PF）至小脑浦肯野细胞（PC）突触处的长时程抑制（LTD）与浦肯野细胞的输出有关，而浦肯野细胞是小脑皮质的唯一输出。除了突触可塑性外，内在兴奋性也是决定浦肯野细胞输出的因素之一。尽管有人提出了内在兴奋性的长时程增强（LTP-IE），但尚未研究PF-PC LTD如何改变浦肯野细胞的内在兴奋性。在这里，我们表明，配对PF和攀缘纤维（CF）以诱导PF-PC LTD会在雄性C57BL/6小鼠的小脑浦肯野细胞中引发LTD-IE。有趣的是，这种内在可塑性表现出与突触可塑性不同的动力学，但两种可塑性形式都共享Ca信号和蛋白激酶C途径作为其潜在机制。尽管小电导Ca激活K通道在LTP-IE中起重要作用，但尚未发现直接关联。在PF-PC LTD诱导后，树突状EPSP的时间总和或动作电位频率适应性的功率均未改变，这表明小脑LTD以定量方式执行信息处理，而不会改变突触整合的质量和输出信号的产生。我们的结果表明，LTD-IE可能通过放大PF突触传递的修饰，与突触抑制对神经元的总净输出产生协同作用。尽管浦肯野细胞（PC）的输出是小脑依赖性学习和记忆的关键组成部分，但突触LTD发生时PC兴奋性的变化尚不清楚。在这里，我们表明PF-PC LTD的诱导会在PC中引发LTD-IE。我们的观察补充了先前内在兴奋性长时程增强（LTP-IE）的内在可塑性现象，为内在可塑性与突触可塑性一样具有双向性的观点提供了证据。LTD-IE与突触LTD同时发生，并且这两种现象均依赖于Ca信号通路。此外，我们的发现提出了这样一种前景，即这种突触和内在可塑性在PC中协同作用，在学习发生时沿相同方向改变神经元活动。
