Fernández de Sevilla David, Cabezas Carolina, de Prada Amaranta N Oshima, Sánchez-Jiménez Abel, Buño Washington
Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avenida Doctor Arce 37, 28002 Madrid, Spain.
J Physiol. 2002 Nov 15;545(1):51-63. doi: 10.1113/jphysiol.2002.029165.
Analysis of the cholinergic regulation of glutamatergic neurotransmission is an essential step in understanding the hippocampus because it can influence forms of synaptic plasticity that are thought to underlie learning and memory. We studied in vitro the cholinergic regulation of excitatory postsynaptic currents (EPSCs) evoked in rat CA1 pyramidal neurons by Schaffer collateral (SC) stimulation. Using "minimal" stimulation, which activates one or very few synapses, the cholinergic agonist carbamylcholine (CCh) increased the failure rate of functional more (36 %) than of silent synapses (7 %), without changes in the EPSC amplitude. These effects of CCh were insensitive to manipulations that increased the probability of release, such as paired pulse facilitation, increases in temperature and increases in the extracellular Ca(2+) : Mg(2+) ratio. Using "conventional" stimulation, which activates a large number of synapses, CCh inhibited more the pharmacologically isolated non-NMDA (86 %) than the NMDA (47 %) EPSC. The changes in failure rate, EPSC variance and the increased paired pulse facilitation that paralleled the inhibition imply that CCh decreased release probability. Muscarine had similar effects. The inhibition by both CCh and by muscarine was prevented by atropine. We conclude that CCh reduces the non-NMDA component of SC EPSCs by selectively inhibiting transmitter release at functional synapses via activation of muscarinic receptors. The results suggest that SCs have two types of terminals, one in functional synapses, selectively sensitive to regulation through activation of muscarinic receptors, and the other in silent synapses less sensitive to that regulation. The specific inhibition of functional synapses would favour activity-dependent plastic phenomena through NMDA receptors at silent synapses without the activation of non-NMDA receptors and functional synapses.
分析胆碱能对谷氨酸能神经传递的调节是理解海马体的关键步骤，因为它会影响被认为是学习和记忆基础的突触可塑性形式。我们在体外研究了通过刺激大鼠CA1锥体神经元的Schaffer侧支（SC）诱发的兴奋性突触后电流（EPSC）的胆碱能调节。使用“最小”刺激（激活一个或极少数突触），胆碱能激动剂氨甲酰胆碱（CCh）增加了功能性突触（36%）而非沉默突触（7%）的失败率，且EPSC幅度无变化。CCh的这些作用对增加释放概率的操作不敏感，如双脉冲易化、温度升高和细胞外Ca(2+)：Mg(2+)比值增加。使用“常规”刺激（激活大量突触），CCh对药理学分离的非NMDA（86%）EPSC的抑制作用比对NMDA（47%）EPSC的抑制作用更强。与抑制作用平行的失败率、EPSC方差变化以及双脉冲易化增加表明CCh降低了释放概率。毒蕈碱有类似作用。CCh和毒蕈碱的抑制作用均被阿托品阻断。我们得出结论，CCh通过激活毒蕈碱受体选择性抑制功能性突触处的递质释放，从而降低SC EPSC的非NMDA成分。结果表明，SC有两种类型的终末，一种在功能性突触中，对通过激活毒蕈碱受体的调节有选择性敏感性，另一种在沉默突触中，对该调节不太敏感。对功能性突触的特异性抑制将有利于通过沉默突触处的NMDA受体而非非NMDA受体和功能性突触的激活产生依赖活动的可塑性现象。
