Factors determining the efficacy of distal excitatory synapses in rat hippocampal CA1 pyramidal neurones
Factors determining the efficacy of distal excitatory synapses in rat hippocampal CA1 pyramidal neurones
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DOI：
10.1111/j.1469-7793.1998.441bt.x
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发表时间：
1998-03-01
影响因子：
5.5
通讯作者：
Lambert, JDC
中科院分区：
文献类型：
--
作者：
Andreasen, M;Lambert, JDC
1.本文报道了一种新的离体大鼠海马脑片的制备方法，分离了对CA_1锥体神经元远端顶树突的突触输入。这已被用于研究远端诱发突触电位的特性.远端成对脉冲刺激（0.1 Hz）诱发的树突状反应，由一对EPSP，这表明易化。第一个EPSP的上升时间（10- 90%）为2.2 +/- 0.05 ms，半宽为9.1 +/- 0.13 ms。CNQX（10 μ M）大大降低了EPSP，其余组分在无Mg 2+的林格氏溶液中可以增强，并被AP 5（50 μ M）阻断。在70%的树突中，EPSP之后是延长的后超极化（AHP），其可以被选择性和有效的GABA（B）拮抗剂CGP 55845 A（2 μ M）阻断。这些结果表明，EPSP主要由非NMDA受体介导，NMDA受体的贡献很小，而AHP是GABA（B）受体介导的慢IPSP。对于体细胞内记录，近端产生的EPSP的上升时间（3.4 +/- 0.1 ms）是远端产生的EPSP（6.7 +/- 0.5 ms）的一半，而半宽相似（分别为19.6 +/- 0.8 ms和23.8 +/- 1 ms）。这些结果表明，通过近端顶端树突的传播减慢了远端产生的EPSP的达峰时间。远端刺激在60%的锥体神经元中诱发棘波。在阈下，远端诱发的锋电位总是出现在树突EPSP的衰减相，表明锋电位是在距离树突记录部位近的某个距离处开始的。此外，远端和近端产生的阈值尖峰具有类似的电压依赖性。因此，这些结果表明，远端产生的阈值尖峰主要在初始段启动。在阈值时，刺激远端突触产生的尖峰从树突状EPSP的衰减阶段产生，其潜伏期由尖峰起始区的EPSP的时间过程决定。然而，最大刺激，尖峰直接从EPSP的峰值产生，尖峰时间与阈下树突状EPSP的尖峰时间相似。功能上：这意味着可以通过募集更多的突触来克服树突传播的影响，从而确保对远端突触输入的更快的响应时间。在42%的远端EPSP诱发棘波的神经元中，EPSP振幅和棘波潜伏期之间的关系可以通过EPSP的恒定树突调制来解释。在其余的58%中，潜伏期的变化大于恒定的树突影响。潜伏期的这种额外变化最好解释为尖峰起始区突然转移到近端树突。这将解释TTX（10 μ M）的躯体应用对逆向诱发的尖峰和远端诱发的阈上尖峰的作用之间观察到的延迟。本研究结果表明，尽管存在Na+和Ca 2+电流，但未实现对主要近端树突的电紧张性的完全补偿。然而，在大多数锥体神经元中，远端兴奋性突触能够启动发放，并且EPSP振幅的变化可以调节发放潜伏期。此外，即使初级锋电位起始区在起始段，结果表明，在生理条件下，它可以移动到近端的顶树突，这是进一步缩短远端兴奋性突触输入的反应时间的效果。
1. A new preparation of the in vitro rat hippocampal slice has been developed in which the synaptic input to the distal apical dendrites of CA1 pyramidal neurones is isolated. This has been used to investigate the properties of distally evoked synaptic potentials.2. Distal paired-pulse stimulation (0.1 Hz) evoked a dendritic response consisting of a pair of EPSPs, which showed facilitation. The first EPSP had rise time (10-90 %) of 2.2 +/- 0.05 ms and a half-width of 9.1 +/- 0.13 ms. The EPSPs were greatly reduced by CNQX (10 mu M) and the remaining component could be enhanced in Mg2+-free Ringer solution and blocked by AP5 (50 mu M). In 70 % of the dendrites, the EPSPs were followed by a prolonged after hyperpolarization (AHP) which could be blocked by a selective and potent GABA(B) antagonist, CGP55845A (2 mu M). These results indicate that the EPSPs are primarily mediated by non NMDA receptors with a small contribution from NMDA receptors, whereas the AHP is a GABA(B) receptor-mediated slow IPSP.3. With intrasomatic recordings, the rise time of proximally generated EPSPs (3.4 +/- 0.1 ms) was half that of distally generated EPSPs (6.7 +/- 0.5 ms), whereas the half-widths were similar (19.6 +/- 0.8 ms and 23.8 +/- 1 ms, respectively). These results indicate that propagation through the proximal apical dendrites slows the time-to-peak of distally generated EPSPs.4. Distal stimulation evoked spikes in 60 % of pyramidal neurones. At threshold, the distally evoked spike always appeared on the decaying phase of the dendritic EPSP, indicating that the spike is initiated at some distance proximal to the dendritic recording site. Furthermore, distally and proximally generated threshold spikes had a similar voltage dependency These results therefore suggest that distally generated threshold spikes are primarily initiated at the initial segment.5. At threshold, spikes generated by stimulation of distal synapses arose from the decaying phase of the dendritic EPSPs with a latency determined by the time course of the EPSP at the spike initiation zone. With maximal stimulation, however, the spikes arose directly from the peak of the EPSPs with a time-to-spike similar to the time-to-peak of subthreshold dendritic EPSPs. Functionally: this means that the effect of dendritic propagation can be, overcome by recruiting more synapses, thereby ensuring a faster response time to distal synaptic inputs.6. In 42 % of the neurones in which distal EPSPs evoked spikes, the relationship between EPSP amplitude and spike latency could be accounted for by a constant dendritic modulation of the EPSP. In the remaining 58 %, the change in latency was, greater than can be accounted for by a constant dendritic influence. This additional change in latency is best explained by a sudden shift in the spike initiation zone to the proximal dendrites. This would explain the delay observed between the action of somatic application of TTX (10 mu M) on antidromically evoked spikes and distally evoked suprathreshold spikes.7. The present results indicate that full compensation for the electrotonic properties of the main proximal dendrites is not achieved despite the presence of Na+ and Ca2+ currents. Nevertheless, distal excitatory synapses are capable of initiating spiking in most pyramidal neurones, and changes in EPSP amplitude can modulate the spike latency. Furthermore, even though the primary spike initiation zone is in the initial segment, the results suggest that it can move into the proximal apical dendrites under physiological conditions, which was the effect of further shortening the response time to distal excitatory synaptic inputs.