LONG-LASTING MODIFICATION OF THE SYNAPTIC PROPERTIES OF RAT CA3 HIPPOCAMPAL-NEURONS INDUCED BY KAINIC ACID
LONG-LASTING MODIFICATION OF THE SYNAPTIC PROPERTIES OF RAT CA3 HIPPOCAMPAL-NEURONS INDUCED BY KAINIC ACID
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DOI：
10.1113/jphysiol.1988.sp017294
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发表时间：
1988-10-01
影响因子：
5.5
通讯作者：
GHO, M
中科院分区：
文献类型：
--
作者：
BENARI, Y;GHO, M
采用细胞内和细胞外记录技术研究了kainic酸短浴（KA, 200-250 nM, 3-5 min）对大鼠海马CA3区的作用。KA诱发的脉冲持续10-15分钟。此外，在KA后，对CA3的各种输入进行电刺激，在控制条件下诱发EPSP- ipsp序列，诱发EPSP随后爆发。这种诱发反应在去除KA后持续了几个小时，这表明CA3神经元的突触特性发生了持久的改变。细胞内记录显示，自发和诱发的脉冲由5到10个动作电位组成，其振幅为10-25 mV，持续时间为40-100 ms。自发放电和诱发放电后均出现振幅为15-25 mV、持续时间为1-1.5 s的长时间超极化。我们认为自发和诱发的同步脉冲都是由一个多突触网络产生的，因为：(a)细胞内记录的脉冲与细胞外场记录的脉冲同步；(b)当钴（1 mM）或TTX （1 .mu）阻断突触传递或Na+动作电位时，脉冲消失。米)分别;(c)二价阳离子浓度升高抑制爆发；(d)破裂的发生与细胞的膜电位无关；(e)脉冲背后的去极化位移是膜电位的线性函数，在0 mV时极性反转。此外，诱发的脉冲是具有可变延迟的全或无事件。自发和诱发的脉冲层流分析表明，它们是由位于CA3锥体细胞树突远端顶端节的突触产生的。诱发的持续爆发既不是由于细胞兴奋性的持续变化，也不是由于gaba能突触抑制的长期减少。高浓度钾（7毫米）的浴液应用也诱导自发和诱发的脉冲；后者在返回对照培养基后仍持续数小时。n -甲基-D-天冬氨酸（NMDA）拮抗剂D- apv （D(-)-2-氨基-5-磷酸戊酸）(30 .mu。M)，不阻断KA或高钾诱导的自发放电，但阻止了对突触反应的持久影响。总之，我们认为突触反应的持久变化是由施加KA或高钾期间和之后不久的自发同步放电产生的。D-APV实验表明NMDA受体参与了这种变化，就像其他形式的长期突触可塑性一样。
The action of a short bath application of kainic acid (KA, 200-250 nM, 3-5 min) on the CA3 region of rat hippocampal slices has been studied with intracellular and extracellular recording techniques. KA evoked bursts which persisted for 10-15 min. In addition, after KA, electrical stimulation of various inputs to CA3 which elicited an EPSP-IPSP sequence in control conditions evoked an EPSP followed by a burst. This evoked response persisted for several hours after removal of KA suggesting the occurrence of a long-lasting modification of the synaptic properties of CA3 neurones. Intracellular recordings showed the spontaneous and evoked bursts to consist of five to ten action potentials riding on a depolarizing shift 10-25 mV in amplitude and 40-100 ms in duration. Both spontaneous and evoked bursts were followed by a long-lasting hyperpolarization 15-25 mV in amplitude and 1-1.5 s in duration. We propose that both spontaneous and evoked synchronized bursts are generated by a polysynaptic network, since: (a) intracellularly recorded bursts were synchronized with the bursts in extracellular field recording; (b) bursts disappeared when synaptic transmission or Na+ action potential were blocked by cobalt (1 mM) or TTX (1 .mu.M) respectively; (c) bursts were suppressed by elevated divalent cation concentration; (d) burst occurrence was independent of the membrane potential of the cell; (e) the depolarization shift that underlies the bursts was a linear function of the membrane potential and reversed in polarity at 0 mV. In addition, the evoked bursts were all-or-none events with a variable latency. Laminar profile analysis of the spontaneous and evoked bursts suggests that they were generated by synapses located on the distal apical segments of the dendrites of CA3 pyramidal cells. The persistence of the evoked bursts was neither due to a persistent change in cell excitability nor to a long-lasting reduction in GABAergic synaptic inhibition. Bath application of a high concentration of potassium (7 mM) also induced spontaneous and evoked bursts; the latter also persisted several hours after return to control medium. The N-methyl-D-aspartate (NMDA) antagonists, D-APV (D(-)-2-amino-5-phosphonovaleric acid) (30 .mu.M), did not block the spontaneous discharges induced by KA or high potassium, but prevented the long-lasting effects on the synaptic responses. In conclusion, we suggest that the long-lasting change of synaptic respones is generated by the spontaneous synchronized discharges present during and shortly after the application of KA or high potassium. D-APV experiments suggest that NMDA receptors are involved in this change as in other forms of long-term synaptic plasticity.