Proulx Eliane, Leshchenko Yevgen, Kokarovtseva Larisa, Khokhotva Vladislav, El-Beheiry Mostafa, Snead O Carter, Perez Velazquez Jose L
Brain and Behaviour Programme and Division of Neurology, The Hospital for Sick Children, Department of Neurology, Room 6535 Hill Wing, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Eur J Neurosci. 2006 Jan;23(2):489-96. doi: 10.1111/j.1460-9568.2005.04558.x.
The synchronized discharges typical of seizures have a multifactorial origin at molecular, cellular and network levels. During recent years, the functional role of gap-junctional coupling has received increased attention as a mechanism that may participate in seizure generation. We have investigated the possible functional roles of thalamic and hippocampal gap-junctional communication (GJC) in the generation of spike-and-wave discharges in a rodent model of atypical absence seizures. Seizures in this model spread throughout limbic, thalamic and neocortical areas. Rats were chronically implanted with cannulae to deliver drugs or saline, and local field potentials recordings were performed using intracerebral electrodes positioned in distinct brain areas. Initially, the effects on synaptic transmission of the gap-junctional blockers used in this study were determined. Neither carbenoxolone (CBX) nor 18-alpha-glycyrrhetinic acid altered chemical synaptic transmission at the concentrations tested. These two compounds, when injected via cannulae into the reticular nucleus of the thalamus (NRT), decreased significantly the duration of seizures as compared with saline injections or injections of the CBX inactive derivative glycyrrhizic acid. CBX injections into the hippocampus resulted in diminished seizure activity as well. NRT injections of trimethylamine, which presumably causes intracellular alkalinization (thereby promoting gap-junctional opening), enhanced seizures and spindle activity. These observations suggest that, in this rodent model, thalamic and limbic areas are involved in the synchronous paroxysmal activity and that GJC contributes to the spike-and-wave discharges.
癫痫发作典型的同步放电在分子、细胞和网络水平上具有多因素起源。近年来，缝隙连接耦合的功能作用作为一种可能参与癫痫发作产生的机制受到了更多关注。我们研究了丘脑和海马缝隙连接通讯（GJC）在非典型失神癫痫啮齿动物模型中棘波和慢波放电产生中的可能功能作用。该模型中的癫痫发作会扩散到边缘系统、丘脑和新皮质区域。大鼠被长期植入套管以给药或生理盐水，并使用置于不同脑区的脑内电极进行局部场电位记录。首先，确定了本研究中使用的缝隙连接阻滞剂对突触传递的影响。在所测试的浓度下，生胃酮（CBX）和18-α-甘草次酸均未改变化学突触传递。当通过套管将这两种化合物注入丘脑网状核（NRT）时，与注射生理盐水或CBX无活性衍生物甘草酸相比，癫痫发作的持续时间显著缩短。向海马注射CBX也导致癫痫活动减弱。向NRT注射三甲胺，推测会导致细胞内碱化（从而促进缝隙连接开放），增强癫痫发作和纺锤波活动。这些观察结果表明，在这个啮齿动物模型中，丘脑和边缘系统区域参与了同步阵发性活动，并且GJC促成了棘波和慢波放电。
