Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul 136-791, Korea.
Neuron. 2011 Apr 14;70(1):95-108. doi: 10.1016/j.neuron.2011.02.042.
Neurons of the reticular thalamus (RT) display oscillatory burst discharges that are believed to be critical for thalamocortical network oscillations related to absence epilepsy. Ca²+-dependent mechanisms underlie such oscillatory discharges. However, involvement of high-voltage activated (HVA) Ca²+ channels in this process has been discounted. We examined this issue closely using mice deficient for the HVA Ca(v)2.3 channels. In brain slices of Ca(v)2.3⁻/⁻, a hyperpolarizing current injection initiated a low-threshold burst of spikes in RT neurons; however, subsequent oscillatory burst discharges were severely suppressed, with a significantly reduced slow afterhyperpolarization (AHP). Consequently, the lack of Ca(v)2.3 resulted in a marked decrease in the sensitivity of the animal to γ-butyrolactone-induced absence epilepsy. Local blockade of Ca(v)2.3 channels in the RT mimicked the results of Ca(v)2.3⁻/⁻ mice. These results provide strong evidence that Ca(v)2.3 channels are critical for oscillatory burst discharges in RT neurons and for the expression of absence epilepsy.
丘脑网状核（RT）神经元表现出爆发性振荡放电，据信这对于与失神性癫痫相关的丘脑皮质网络振荡至关重要。这种振荡放电的基础是钙依赖性机制。然而，高电压激活（HVA）钙通道在这个过程中的参与已被否定。我们使用缺乏 HVA Ca(v)2.3 通道的小鼠仔细研究了这个问题。在 Ca(v)2.3⁻/⁻脑片中，超极化电流注入会引发 RT 神经元的低阈值爆发；然而，随后的振荡爆发放电受到严重抑制，慢后超极化（AHP）明显减少。因此，缺乏 Ca(v)2.3 导致动物对 γ-丁内酯诱导的失神性癫痫的敏感性显著降低。在 RT 中局部阻断 Ca(v)2.3 通道模拟了 Ca(v)2.3⁻/⁻小鼠的结果。这些结果提供了有力的证据，表明 Ca(v)2.3 通道对于 RT 神经元的爆发性振荡放电以及失神性癫痫的表达至关重要。
