Frantseva M V, Perez Velazquez J L, Carlen P L
Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.
J Neurophysiol. 1998 Sep;80(3):1317-26. doi: 10.1152/jn.1998.80.3.1317.
Free radical (FR) production was linked to the generation of epileptiform activity. We performed electrophysiological recordings in rat thalamocortical slices to investigate the effects of FRs on the intrinsic and synaptic properties of thalamic and cortical neurons. Whole cell recordings from identified cortical pyramidal neurons and thalamic neurons of the ventrobasal nucleus revealed that exposure to the FR-forming agent H2O2 (2.5 mM) decreased gamma-aminobutyric acid-A- and gamma-aminobutyric acid-B-mediated inhibition to 35.3 +/- 13.4% and 13.7 +/- 4.4% (means +/- SE) of control in cortical neurons and to 41.8 +/- 14.8% and 33.6 +/- 11.6% of control in thalamic neurons. H2O2 application increased excitatory transmission in thalamic neurons to 162.9 +/- 29.6% of control but caused no change in cortical neurons. H2O2 altered significantly the characteristic low-pass filter behavior of cortical and thalamic cells as determined by their input impedances. After 35 min of superfusion, the impedance of cortical neurons decreased by 67.0 +/- 14.5%, and thalamic decreased by 76.3 +/- 2.7% for the frequencies in the range 1-50 Hz while remaining constant for frequencies > 200 Hz. Neuronal hyperexcitability was manifested during H2O2 exposure by continuous firing and long depolarizing shifts in response to extracellular stimulation in both thalamocortical and cortical neurons only in slices preserving thalamocortical connections. In slices with severed thalamocortical connections, cortical neurons did not show signs of hyperexcitability. These observations indicate that FRs could promote hyperexcitability of thalamocortical circuits by altering the balance between excitation and inhibition and by transforming the characteristic low-pass filter behavior into a flat band-pass filter.
自由基（FR）的产生与癫痫样活动的发生有关。我们在大鼠丘脑皮质切片上进行了电生理记录，以研究FR对丘脑和皮质神经元的内在特性及突触特性的影响。对已识别的皮质锥体神经元和腹侧基底核丘脑神经元进行全细胞记录发现，暴露于产生活性氧的试剂过氧化氢（2.5 mM）后，皮质神经元中γ-氨基丁酸A和γ-氨基丁酸B介导的抑制作用分别降至对照的35.3±13.4%和13.7±4.4%（平均值±标准误），丘脑神经元中则降至对照的41.8±14.8%和33.6±11.6%。施加过氧化氢使丘脑神经元的兴奋性突触传递增加至对照的162.9±29.6%，但对皮质神经元无影响。过氧化氢显著改变了皮质和丘脑细胞由输入阻抗所决定的特征性低通滤波行为。灌流35分钟后，对于1 - 50 Hz范围内的频率，皮质神经元的阻抗降低了67.0±14.5%，丘脑神经元降低了76.3±2.7%，而对于频率>200 Hz的情况则保持不变。仅在保留丘脑皮质连接的切片中，在过氧化氢暴露期间，丘脑皮质和皮质神经元通过持续放电以及对细胞外刺激的长时去极化偏移表现出神经元兴奋性过高。在丘脑皮质连接切断的切片中，皮质神经元未表现出兴奋性过高的迹象。这些观察结果表明，自由基可通过改变兴奋与抑制之间的平衡以及将特征性低通滤波行为转变为平坦带通滤波行为来促进丘脑皮质回路的兴奋性过高。
