N-methyl-D-Aspartate Receptors Contribute to Complex Spike Signaling in Cerebellar Purkinje Cells: An In vivo Study in Mice.
N-methyl-D-Aspartate Receptors Contribute to Complex Spike Signaling in Cerebellar Purkinje Cells: An In vivo Study in Mice.
复制标题
N-甲基-D-天冬氨酸受体有助于小脑浦肯野细胞中复杂的尖峰信号传导：小鼠体内研究。
DOI：
10.3389/fncel.2016.00172
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发表时间：
2016
影响因子：
5.3
通讯作者：
Qiu DL
中科院分区：
文献类型：
--
作者：
Liu H;Lan Y;Bing YH;Chu CP;Qiu DL
N-甲基-D-天冬氨酸受体（NMDARs）在成年小鼠小脑皮质中的爬行纤维-浦肯野细胞（CF-PC）突触处突触后表达，并在体外条件下参与CF-PC突触传递。本研究采用在体全细胞记录技术和药理学方法，研究了NMDARs在大鼠小脑皮层自发复合放电（complex spike，CS）过程中CF-PC突触的作用。在电流钳条件下，小脑表面应用NMDA（50 μM）可引起CS诱发的简单锋电位（SS）放电暂停增加，同时伴有SS放电频率降低。在电压钳条件下，NMDA可增强CS诱发的内向电流波形，表现为自发CS的曲线下面积（AUC）和小穗数增加。NMDA浓度依赖性地增加自发CS的AUC。NMDA增加自发CS AUC的EC 50为33.4 μM。此外，NMDA显著增加CS诱发的后超极化（AHP）电流的幅度，半宽度和衰减时间。用D-（-）-2-氨基-5-磷酸戊酸（D-APV，250 μM）阻断NMDAR可降低AHP电流的AUC、小穗数和振幅。阻断α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体后，不能观察到NMDA对CS活性的增强作用。结果表明，CF-PC突触的NMDAR通过增强CS诱发的内向电流和AHP电流参与了CS的自发活动。
N-methyl-D-aspartate receptors (NMDARs) are post-synaptically expressed at climbing fiber-Purkinje cell (CF-PC) synapses in cerebellar cortex in adult mice and contributed to CF-PC synaptic transmission under in vitro conditions. In this study, we investigated the role of NMDARs at CF-PC synapses during the spontaneous complex spike (CS) activity in cerebellar cortex in urethane-anesthetized mice, by in vivo whole-cell recording technique and pharmacological methods. Under current-clamp conditions, cerebellar surface application of NMDA (50 μM) induced an increase in the CS-evoked pause of simple spike (SS) firing accompanied with a decrease in the SS firing rate. Under voltage-clamp conditions, application of NMDA enhanced the waveform of CS-evoked inward currents, which expressed increases in the area under curve (AUC) and spikelet number of spontaneous CS. NMDA increased the AUC of spontaneous CS in a concentration-dependent manner. The EC50 of NMDA for increasing AUC of spontaneous CS was 33.4 μM. Moreover, NMDA significantly increased the amplitude, half-width and decay time of CS-evoked after-hyperpolarization (AHP) currents. Blockade of NMDARs with D-(-)-2-amino-5-phosphonopentanoic acid (D-APV, 250 μM) decreased the AUC, spikelet number, and amplitude of AHP currents. In addition, the NMDA-induced enhancement of CS activity could not be observed after α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors were blocked. The results indicated that NMDARs of CF-PC synapses contributed to the spontaneous CS activity by enhancing CS-evoked inward currents and AHP currents.