Destexhe A
Neurophysiology Laboratory, Department of Physiology, Laval University, Québec G1K 7P4, Canada.
J Neurosci. 1998 Nov 1;18(21):9099-111. doi: 10.1523/JNEUROSCI.18-21-09099.1998.
Neocortical and thalamic neurons are involved in the genesis of generalized spike-and-wave (SW) epileptic seizures. The cellular mechanism of SW involves complex interactions between intrinsic neuronal firing properties and multiple types of synaptic receptors, but because of the complexity of these interactions the exact details of this mechanism are unclear. In this paper these types of interactions were investigated by using biophysical models of thalamic and cortical neurons. It is shown first that, because of the particular activation properties of GABAB receptor-mediated responses, simulated field potentials can display SW waveforms if cortical pyramidal cells and interneurons generate prolonged discharges in synchrony, without any other assumptions. Here the "spike" component coincided with the synchronous firing, whereas the "wave" component was generated mostly by slow GABAB-mediated K+ currents. Second, the model suggests that intact thalamic circuits can be forced into a approximately 3 Hz oscillatory mode by corticothalamic feedback. Here again, this property was attributable to the characteristics of GABAB-mediated inhibition. Third, in the thalamocortical system this property can lead to generalized approximately 3 Hz oscillations with SW field potentials. The oscillation consisted of a synchronous prolonged firing in all cell types, interleaved with a approximately 300 msec period of neuronal silence, similar to experimental observations during SW seizures. This model suggests that SW oscillations can arise from thalamocortical loops in which the corticothalamic feedback indirectly evokes GABAB-mediated inhibition in the thalamus. This mechanism is shown to be consistent with a number of different experimental models, and experiments are suggested to test its consistency.
新皮质和丘脑神经元参与全身性棘波-慢波（SW）癫痫发作的发生。SW的细胞机制涉及内在神经元放电特性与多种类型突触受体之间的复杂相互作用，但由于这些相互作用的复杂性，该机制的确切细节尚不清楚。在本文中，通过使用丘脑和皮质神经元的生物物理模型对这些类型的相互作用进行了研究。首先表明，由于GABAB受体介导反应的特定激活特性，如果皮质锥体细胞和中间神经元同步产生长时间放电，模拟场电位可显示SW波形，无需任何其他假设。这里的“棘波”成分与同步放电一致，而“慢波”成分主要由缓慢的GABAB介导的K+电流产生。其次，该模型表明，完整的丘脑回路可通过皮质丘脑反馈被迫进入约3Hz的振荡模式。同样，该特性归因于GABAB介导的抑制的特征。第三，在丘脑皮质系统中，该特性可导致具有SW场电位的全身性约3Hz振荡。该振荡由所有细胞类型的同步长时间放电组成，其间穿插约300毫秒的神经元沉默期，类似于SW发作期间的实验观察结果。该模型表明，SW振荡可源于丘脑皮质环路，其中皮质丘脑反馈间接诱发丘脑中GABAB介导的抑制。该机制被证明与许多不同的实验模型一致，并建议进行实验以测试其一致性。
