Electrophysiology of CA1 pyramidal neurons in an animal model of neuronal migration disorders: Prenatal methylazoxymethanol treatment
Electrophysiology of CA1 pyramidal neurons in an animal model of neuronal migration disorders: Prenatal methylazoxymethanol treatment
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DOI：
10.1016/0920-1211(95)00045-3
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发表时间：
1995-10-01
影响因子：
2.2
通讯作者：
Schwartzkroin, PA
中科院分区：
文献类型：
--
作者：
Baraban, SC;Schwartzkroin, PA
产前注射甲基甲氧甲醇醋酸酯（MAMac）破坏发育中的大鼠细胞迁移。我们研究了接受mamac治疗的幼龄动物（出生后25-35天）海马CA1锥体神经元的电生理特征。经mamac处理的组织中CA1细胞的体外细胞内记录显示，静息膜电位（平均值，-61.5 +/- 1.5 mV）、动作电位振幅（平均值，69 +/- 3.1 mV）、动作电位持续时间（平均值，2.1 +/- 0.2 ms）、输入电阻（平均值，51.5 +/- 3.6 M ω）和时间常数（平均值，33.2 +/- 1.2 ms）与对照组织中的CA1细胞相似。然而，经mamac处理的组织可以被区分为具有更高百分比的细胞（62%对10%），这些细胞在响应阈值以上电流注射时触发动作电位爆发。CA1细胞在mamac处理和对照组织中的突触反应具有可比性。在所有测试的刺激强度（50-1500 mu A）下，CA1对刺激的场响应也具有可比性。在所有经mamac处理的切片中，细胞外钾浓度（[K+](0)）从3mm升高到6mm，导致辐射层刺激反应中癫痫样放电活动（10/10），但只有三分之一的对照组（3/9）。大多数（8/13）经mamac处理的切片在6 mM KCI中也观察到自发性癫痫样放电，但没有对照组。这些数据表明，胎儿发育期间的MAMac治疗不仅破坏了正常的解剖组织，而且导致海马CA1锥体细胞区域电生理特征的改变。因此，MAMac模型可以提供与发育异常相关的早发性癫痫综合征的见解。
Prenatal methylazoxymethanol acetate (MAMac) injection disrupts cell migration in developing rats. We investigated the electrophysiological characteristics of hippocampal CA1 pyramidal neurons from young MAMac-treated animals (postnatal days 25-35). In vitro intracellular recordings from CA1 cells in MAMac-treated tissue revealed resting membrane potential (mean, -61.5 +/- 1.5 mV), action potential amplitude (mean, 69 +/- 3.1 mV), action potential duration (mean, 2.1 +/- 0.2 ms), input resistance (mean, 51.5 +/- 3.6 M Omega) and time constant (mean, 33.2 +/- 1.2 ms) similar to those of CA1 cells from control tissue. However, MAMac-treated tissue could be distinguished as having a higher percentage of cells (62% vs. 10%) which fire a burst of action potentials in response to suprathreshold current injection. The synaptic responses of CA1 cells in MAMac-treated and control tissue were comparable. The CA1 field response to stimulation was also comparable at all stimulus intensities tested (50-1500 mu A). Elevation of extracellular potassium concentration ([K+](0)) from 3 mM to 6 mM resulted in epileptiform discharge activity in response to stratum radiatum stimulation in all MAMac-treated slices (10/10) but in only one-third of controls (3/9). Spontaneous epileptiform discharges were also observed in the majority (8/13) of MAMac-treated slices bathed in 6 mM KCI but in no controls. These data suggest that MAMac treatment during fetal development not only disrupts normal anatomical organization but also leads to alterations in electrophysiological features of the hippocampal CA1 pyramidal cell region. As such, the MAMac model may provide insights into early onset seizure syndromes associated with developmental abnormalities.