Gao T M, Pulsinelli W A, Xu Z C
Department of Neurology, University of Tennessee at Memphis, 38163, USA.
Neuroscience. 1998 Nov;87(2):371-83. doi: 10.1016/s0306-4522(98)00150-x.
Evoked postsynaptic potentials of CA1 pyramidal neurons in rat hippocampus were studied during 48 h after severe ischemic insult using in vivo intracellular recording and staining techniques. Postischemic CA1 neurons displayed one of three distinct response patterns following contralateral commissural stimulation. At early recirculation times (0-12 h) approximately 50% of neurons exhibited, in addition to the initial excitatory postsynaptic potential, a late depolarizing postsynaptic potential lasting for more than 100 ms. Application of dizocilpine maleate reduced the amplitude of late depolarizing postsynaptic potential by 60%. Other CA1 neurons recorded in this interval failed to develop late depolarizing postsynaptic potentials but showed a modest blunting of initial excitatory postsynaptic potentials (non-late depolarizing postsynaptic potential neuron). The proportion of recorded neurons with late depolarizing postsynaptic potential characteristics increased to more than 70% during 13-24 h after reperfusion. Beyond 24 h reperfusion, approximately 20% of CA neurons exhibited very small excitatory postsynaptic potentials even with maximal stimulus intensity. The slope of the initial excitatory postsynaptic potentials in late depolarizing postsynaptic potential neurons increased to approximately 150% of control values up to 12 h after reperfusion indicating a prolonged enhancement of synaptic transmission. In contrast, the slope of the initial excitatory postsynaptic potentials in non-late depolarizing postsynaptic potential neurons decreased to less than 50% of preischemic values up to 24 h after reperfusion indicating a prolonged depression of synaptic transmission. More late depolarizing postsynaptic potential neurons were located in the medial portion of CA1 zone where neurons are more vulnerable to ischemia whereas more non-late depolarizing postsynaptic potential neurons were located in the lateral portion of CA1 zone where neurons are more resistant to ischemia. The result from the present study suggests that late depolarizing postsynaptic potential and small excitatory postsynaptic potential neurons may be irreversibly injured while non-late depolarizing postsynaptic potential neurons may be those that survive the ischemic insult. Alterations of synaptic transmission may be associated with the pathogenesis of postischemic neuronal injury.
采用体内细胞内记录和染色技术，在严重缺血性损伤后48小时内，对大鼠海马CA1锥体神经元的诱发突触后电位进行了研究。在对侧联合刺激后，缺血后的CA1神经元表现出三种不同反应模式之一。在再灌注早期（0 - 12小时），除了初始兴奋性突触后电位外，约50%的神经元还表现出持续超过100毫秒的晚期去极化突触后电位。应用马来酸氯氮平可使晚期去极化突触后电位的幅度降低60%。在此时间段记录的其他CA1神经元未产生晚期去极化突触后电位，但初始兴奋性突触后电位略有减弱（非晚期去极化突触后电位神经元）。在再灌注后13 - 24小时内，具有晚期去极化突触后电位特征的记录神经元比例增加到70%以上。再灌注超过24小时后，即使给予最大刺激强度，约20%的CA神经元表现出非常小的兴奋性突触后电位。晚期去极化突触后电位神经元的初始兴奋性突触后电位斜率在再灌注后12小时内增加到对照值的约150%，表明突触传递的持续增强。相比之下，非晚期去极化突触后电位神经元的初始兴奋性突触后电位斜率在再灌注后24小时内降至缺血前值的不到50%，表明突触传递的持续抑制。更多的晚期去极化突触后电位神经元位于CA1区的内侧部分，该区域的神经元对缺血更敏感，而更多的非晚期去极化突触后电位神经元位于CA1区的外侧部分，该区域的神经元对缺血更具抵抗力。本研究结果表明，晚期去极化突触后电位和小兴奋性突触后电位神经元可能受到不可逆损伤，而非晚期去极化突触后电位神经元可能是在缺血性损伤中存活下来的神经元。突触传递的改变可能与缺血后神经元损伤的发病机制有关。
