Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Epilepsia. 2011 Dec;52(12):2344-55. doi: 10.1111/j.1528-1167.2011.03312.x. Epub 2011 Nov 16.
Seizure-like activities generated in anterior cingulate cortex (ACC) are usually classified as simple partial and are associated with changes in autonomic function, motivation, and thought. Previous studies have shown that thalamic inputs can modulate ACC seizure, but the exact mechanisms have not been studied thoroughly. Therefore, we investigated the role of thalamic inputs in modulating ACC seizure-like activities. In addition, seizure onset and propagation are difficult to determine in vivo in ACC. We studied the spatiotemporal changes in epileptiform activity in this cortex in a thalamic-ACC slice to clearly determine seizure onset.
We used multielectrode array (MEA) recording and calcium imaging to investigate the modulatory effect of thalamic inputs in a thalamic-ACC slice preparation.
Seizure-like activities induced with 4-aminopyridine (4-AP; 250 μm) and bicuculline (5-50 μm) in ACC were attenuated by glutamate receptor antagonists, and the degree of disinhibition varied with the dose of bicuculline. Seizure-like activities were decreased with 1 Hz thalamic stimulation, whereas corpus callosum stimulation could increase ictal discharges. Amplitude and duration of cingulate seizure-like activities were augmented after removing thalamic inputs, and this effect was not observed with those induced with elevated bicuculline (50 μm). Seizure-like activities were initiated in layers II/III and, after thalamic lesions, they occurred mainly in layers V/VI. Two-dimensional current-source density analyses revealed sink signals more frequently in layers V/VI after thalamic lesions, indicating that these layers produce larger excitatory synchronization. Calcium transients were synchronized after thalamic lesions suggesting that ACC seizure-like activities are subjected to desynchronizing modulation by thalamic inputs. Therefore, ACC seizure-like activities are subject to desynchronizing modulation from medial thalamic inputs to deep layer pyramidal neurons.
Cingulate seizure-like activities were modulated significantly by thalamic inputs. Repeated stimulation of the thalamus efficiently inhibited epileptiform activity, demonstrating that the desynchronization was pathway-specific. The clinical implications of deep thalamic stimulation in the modulation of cingulate epileptic activity require further investigation.
在前扣带回皮层（ACC）中产生的类似于癫痫发作的活动通常被归类为简单部分性癫痫发作，并与自主功能、动机和思维的变化有关。先前的研究表明，丘脑输入可以调节 ACC 癫痫发作，但确切的机制尚未得到充分研究。因此，我们研究了丘脑输入在调节 ACC 样癫痫发作活动中的作用。此外，在 ACC 中，癫痫发作的起始和传播很难在体内确定。我们在丘脑-ACC 切片中研究了该皮质中癫痫样活动的时空变化，以清楚地确定癫痫发作的起始。
我们使用多电极阵列（MEA）记录和钙成像来研究丘脑输入在丘脑-ACC 切片制备中的调制作用。
用 4-氨基吡啶（4-AP；250μm）和荷包牡丹碱（5-50μm）在 ACC 中诱导的类似于癫痫发作的活动被谷氨酸受体拮抗剂减弱，并且抑制程度随荷包牡丹碱剂量的变化而变化。1Hz 丘脑刺激可降低类似于癫痫发作的活动，而胼胝体刺激可增加癫痫发作放电。去除丘脑输入后，ACC 样癫痫发作的幅度和持续时间增加，而用升高的荷包牡丹碱（50μm）诱导时则没有观察到这种效应。类似于癫痫发作的活动起始于 II/III 层，并且在丘脑损伤后，它们主要发生在 V/VI 层。二维电流源密度分析显示，在丘脑损伤后，在 V/VI 层中更频繁地出现汇信号，这表明这些层产生更大的兴奋性同步。钙瞬变在丘脑损伤后被同步，表明 ACC 样癫痫发作活动受到来自内侧丘脑输入的去同步调制。因此，ACC 样癫痫发作活动受到来自内侧丘脑输入到深层锥体神经元的去同步调制。
丘脑输入对扣带回样癫痫发作活动有显著的调节作用。丘脑的重复刺激有效地抑制了癫痫样活动，表明去同步是特定于通路的。深部丘脑刺激在调节扣带回癫痫活动中的临床意义需要进一步研究。
