Hashimoto K, Kano M
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University.
Clin Calcium. 2001 Nov;11(11):1432-9.
Elevation of intracellular calcium concentration (Ca(2+)) induces several forms of long-term synaptic plasticity in cerebellar Purkinje cells (PCs). These include (1) long-term depression (LTD) at parallel fiber (PF) to PC synapses, (2) LTD at climbing fiber (CF) to PC synapses, (3) long-term potentiation (LTP) at synapses from inhibitory interneurons (rebound potentiation). The current knowledge about calcium dependency for these forms of synaptic plasticity is described in this chapter. (1) Induction of PF-LTD is dependent on elevation of Ca(2+), that derives from two distinct sources. One is through voltage-dependent calcium channel (VDCC). A CF stimulation leads to elevation of Ca(2+) due to activation of VDCCs. The other is from the internal calcium store. PFs stimulation activates metabotropic glutamate receptor subtype 1 (mGluR1). It leads to production of inositol-1,4,5-triphosphate (IP(3)) and diacylglycerol (DG) which cause calcium release from internal stores and activation of protein kinase C, respectively. The conjunctive activation of PF and CF inputs is necessary for PF-LTD. (2) LTD at CF to PC synapses (CF-LTD) is induced by the mechanisms similar to those involved in PF-LTD. CF-LTD requires elevation of Ca(2+) and activation of the mGluR1 to PKC cascade. (3) Rebound potentiation is induced by transient elevation of Ca(2+) due to activation of VDCCs or IP3-mediated calcium release from internal stores. Elevation of Ca(2+) activates calcium/ calmodulin-dependent protein kinase II and leads to persistent up-regulation of postsynaptic GABAA receptor function. At the three types of synapses described above, elevation of Ca(2+) also causes short-term depression of neurotransmitter release from presynaptic terminals. Recent studies demonstrate that transient elevation of Ca(2+) produces endocannabinoids in PCs that act retrogradely onto presynaptic terminals and suppress neurotransmitter release.
细胞内钙浓度（[Ca(2+)]i）升高可诱导小脑浦肯野细胞（PCs）产生多种形式的长期突触可塑性。这些包括：（1）平行纤维（PF）与PC突触处的长期抑制（LTD）；（2）攀缘纤维（CF）与PC突触处的LTD；（3）抑制性中间神经元突触处的长期增强（LTP）（反弹增强）。本章将介绍目前关于这些突触可塑性形式的钙依赖性的知识。（1）PF-LTD的诱导依赖于[Ca(2+)]i的升高，其来源于两个不同的来源。一个是通过电压依赖性钙通道（VDCC）。CF刺激由于VDCC的激活导致[Ca(2+)]i升高。另一个来自细胞内钙库。PF刺激激活代谢型谷氨酸受体1亚型（mGluR1）。它导致肌醇-1,4,5-三磷酸（IP(3)）和二酰基甘油（DG）的产生，分别引起细胞内钙库释放钙和激活蛋白激酶C。PF和CF输入的联合激活是PF-LTD所必需的。（2）CF与PC突触处的LTD（CF-LTD）是由与PF-LTD相似的机制诱导的。CF-LTD需要[Ca(2+)]i升高和mGluR1到PKC级联的激活。（3）反弹增强是由VDCC激活或IP3介导的细胞内钙库钙释放引起的[Ca(2+)]i短暂升高所诱导的。[Ca(2+)]i升高激活钙/钙调蛋白依赖性蛋白激酶II，并导致突触后GABAA受体功能的持续上调。在上述三种突触类型中，[Ca(2+)]i升高还会导致突触前终末神经递质释放的短期抑制。最近的研究表明，[Ca(2+)]i的短暂升高会在PCs中产生内源性大麻素，其逆行作用于突触前终末并抑制神经递质释放。
