FACILITATION OF AN NMDA RECEPTOR-MEDIATED EPSP BY PAIRED-PULSE STIMULATION IN RAT NEOCORTEX VIA DEPRESSION OF GABAERGIC IPSPS
FACILITATION OF AN NMDA RECEPTOR-MEDIATED EPSP BY PAIRED-PULSE STIMULATION IN RAT NEOCORTEX VIA DEPRESSION OF GABAERGIC IPSPS
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DOI：
10.1113/jphysiol.1994.sp020443
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发表时间：
1994-12-01
影响因子：
5.5
通讯作者：
ASHE, JH
中科院分区：
文献类型：
--
作者：
METHERATE, R;ASHE, JH
1. 本研究获得了全细胞全密封的活体和体外听觉皮层记录，以研究配对脉冲传入刺激对n -甲基- d-天冬氨酸（NMDA）受体介导的突触活性的影响。在尿素麻醉大鼠（37℃）或体外保存的皮质切片（32℃）的记录中，传入刺激引起单突触早期EPSP和多突触早期和晚期ipsp。此外，当刺激前有一个相同的启动刺激（间隔约200 ms）时，可以诱发晚EPSP。NMDA受体拮抗剂dl -2-氨基-5-磷酸戊酸酯（APV, 50 μ M）可减弱晚期EPSP。γ -氨基丁酸-B （GABA(B)）受体拮抗剂3-氨基-2（4-氯苯基）-2-羟基丙基磺酸（2-OH-saclofen; 50 μ M）可减轻晚期IPSP，并明确显示晚期EPSP。然而，2-OH-saclofen对配对脉冲刺激时引发的第二晚EPSP的影响较小。2-OH-saclofen的膜去极化增加了早期IPSP的大小，再次抑制了晚期EPSP。由于药物阻断EPSP显示单突触诱导的早期和晚期ipsp的成对脉冲抑制，这些数据表明：(1)早期和晚期ipsp都能够抑制晚期EPSP，(2)这些作用在成对脉冲刺激下减弱。晚期EPSP的药理学分离允许测试成对脉冲刺激的直接效果。应用6-氰基-7-硝基喹啉-2,3-二酮（CNQX， 20亩M）、微毒素（10亩M）和2-OH-saclofen（50亩M）分离晚期EPSP（起效3 ms，峰潜伏期28 ms，峰幅7 mV，持续时间240 ms）， EPSP随着膜去极化而增强，APV大部分阻断（约90%），配对脉冲刺激使分离的晚期EPSP抑制30% 5。因此，后期EPSP的明显成对脉冲促进可归因于gaba能抑制的释放，而不是直接促进。后期EPSP的促进是IPSP抑郁的功能后果。结果表明，抑制在调节NMDA受体介导的突触活性中的重要性。
1. Tight seal, whole-cell recordings from auditory cortex in vivo and in vitro were obtained to investigate modification of N-methyl-D-aspartate (NMDA) receptor-mediated synaptic activity by paired-pulse afferent stimulation.2. In recordings from urethane-anaesthetized rats (at 37 degrees C), or from cortical slices maintained in vitro (32 degrees C), afferent stimulation elicited a monosynaptic early EPSP and polysynaptic early and late IPSPs. In addition, a late EPSP could be elicited when the stimulus was preceded by an identical priming stimulus (interval similar to 200 ms). The late EPSP was attenuated by the NMDA receptor antagonist DL-2-amino-5-phosphono-valerate (APV, 50 mu M).3. Bath application of the gamma-aminobutyric acid-B (GABA(B)) receptor antagonist 3-amino-2(4-chlorophenyl)-2-hydroxy-propylsulphonic acid (2-OH-saclofen; 50 mu M) attenuated the late IPSP and clearly revealed a late EPSP. However, 2-OH-saclofen had lesser effects on the second late EPSP elicited during: paired-pulse stimulation. Membrane depolarization in 2-OH-saclofen increased the magnitude of the early IPSP, which suppressed the late EPSP once again. Since pharmacological blockade of EPSPs revealed paired-pulse depression of monosynaptically elicited early and late IPSPs, these data indicate that (1) both early and late IPSPs were capable of suppressing the late EPSP, and (2) these effects were reduced during paired-pulse stimulation.4. Pharmacological isolation of the late EPSP allowed testing of the direct effect of paired-pulse stimulation. Application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 mu M, picrotoxin (10 mu M) and 2-OH-saclofen (50 mu M) isolated the late EPSP (onset, 3 ms; peak latency, 28 ms; peak amplitude, 7 mV; duration, 240 ms), which grew in magnitude with membrane depolarization and was largely (> 90%) blocked by APV, Paired-pulse stimulation depressed the isolated late EPSP by 30%.5. Thus, apparent paired-pulse facilitation of the late EPSP is attributable to release from GABAergic inhibition, and not to direct facilitation. Facilitation of the late EPSP is a functional consequence of IPSP depression. The results indicate the importance of inhibition in regulating synaptic activity mediated by NMDA receptors.