Morin F, Beaulieu C, Lacaille J C
Centre de Recherche en Sciences Neurologiques, Université de Montréal, Montréal, Québec H3C 3J7 Canada.
J Neurophysiol. 1998 Dec;80(6):2836-47. doi: 10.1152/jn.1998.80.6.2836.
Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. J. Neurophysiol. 80: 2836-2847, 1998. Hippocampal sclerosis and hyperexcitability are neuropathological features of human temporal lobe epilepsy that are reproduced in the kainic acid (KA) model of epilepsy in rats. To assess directly the role of inhibitory interneurons in the KA model, the membrane and synaptic properties of interneurons located in 1) stratum oriens near the alveus (O/A) and 2) at the border of stratum radiatum and stratum lacunosum-moleculare (LM), as well as those of pyramidal cells, were examined with whole cell recordings in slices of control and KA-lesioned rats. In current-clamp recordings, intrinsic cell properties such as action potential amplitude and duration, amplitude of fast and medium duration afterhyperpolarizations, membrane time constant, and input resistance were generally unchanged in all cell types after KA treatment. In voltage-clamp recordings, the amplitude and conductance of pharmacologically isolated excitatory postsynaptic currents (EPSCs) were significantly reduced in LM interneurons of KA-treated animals but were not significantly changed in O/A and pyramidal cells. The rise time of EPSCs was not significantly changed in any cell type after KA treatment. In contrast, the decay time constant of EPSCs was significantly faster in O/A interneurons of KA-treated rats but was unchanged in LM and pyramidal cells. The amplitude and conductance of pharmacologically isolated gamma-aminobutyric acid-A (GABAA) inhibitory postsynaptic currents (IPSCs) were not significantly changed in any cell type of KA-treated rats. The rise time and decay time constant of GABAA IPSCs were significantly faster in pyramidal cells of KA-treated rats but were not significantly changed in O/A and LM interneurons. These results suggest that complex alterations in synaptic currents occur in specific subpopulations of inhibitory interneurons in the CA1 region after KA lesions. A reduction of evoked excitatory drive onto inhibitory cells located at the border of stratum radiatum and stratum lacunosum-moleculare may contribute to disinhibition and polysynaptic epileptiform activity in the CA1 region. Compensatory changes, involving excitatory synaptic transmission on other interneuron subtypes and inhibitory synaptic transmission on pyramidal cells, may also take place and contribute to the residual, functional monosynaptic inhibition observed in principal cells after KA treatment.
海藻酸处理后海马CA1区中间神经元突触特性的细胞特异性改变。《神经生理学杂志》80: 2836 - 2847, 1998年。海马硬化和兴奋性过高是人类颞叶癫痫的神经病理学特征，在大鼠的海藻酸（KA）癫痫模型中也会出现。为了直接评估抑制性中间神经元在KA模型中的作用，在对照大鼠和KA损伤大鼠的脑片中，用全细胞记录法检测了位于1）靠近海马槽的海马下托（O/A）和2）放射层与分子层-腔隙层边界（LM）的中间神经元以及锥体细胞的膜和突触特性。在电流钳记录中，KA处理后所有细胞类型的内在细胞特性，如动作电位幅度和持续时间、快速和中等持续时间的超极化后电位幅度、膜时间常数和输入电阻通常没有变化。在电压钳记录中，KA处理动物的LM中间神经元中，药理学分离的兴奋性突触后电流（EPSC）的幅度和电导显著降低，但在O/A中间神经元和锥体细胞中没有显著变化。KA处理后，任何细胞类型的EPSC上升时间均无显著变化。相反，KA处理大鼠的O/A中间神经元中，EPSC衰减时间常数显著加快，但在LM中间神经元和锥体细胞中没有变化。KA处理大鼠的任何细胞类型中，药理学分离的γ-氨基丁酸-A（GABAA）抑制性突触后电流（IPSC）的幅度和电导均无显著变化。KA处理大鼠的锥体细胞中，GABAA IPSC的上升时间和衰减时间常数显著加快，但在O/A中间神经元和LM中间神经元中没有显著变化。这些结果表明，KA损伤后CA1区抑制性中间神经元的特定亚群中出现了突触电流的复杂改变。投射到位于放射层与分子层-腔隙层边界的抑制性细胞上的诱发兴奋性驱动减少，可能导致CA1区去抑制和多突触癫痫样活动。涉及其他中间神经元亚型的兴奋性突触传递和锥体细胞的抑制性突触传递的代偿性变化也可能发生，并导致KA处理后在主细胞中观察到的残余功能性单突触抑制。
