Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic-anterior cingulate slice
Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic-anterior cingulate slice
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DOI：
10.1111/j.1528-1167.2011.03312.x
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发表时间：
2011-12-01
期刊：
影响因子：
5.6
通讯作者：
Shyu, Bai-Chuang
中科院分区：
文献类型：
--
作者：
Chang, Wei-Pang;Wu, Jiun-Shian;Shyu, Bai-Chuang
目的：扣带回前皮质(ACC)产生的癫痫样活动通常被归类为单纯性部分性活动，与自主神经功能、动机和思维的改变有关。以前的研究表明，丘脑输入可以调节ACC发作，但确切的机制还没有得到彻底的研究。因此，我们研究了丘脑输入在调节ACC癫痫样活动中的作用。此外，在ACC中，癫痫的发作和传播很难在体内确定。方法：采用多电极阵列(MEA)记录和钙成像技术研究丘脑-ACC脑片中丘脑传入物质对癫痫样活动的调节作用。主要发现：谷氨酸受体拮抗剂可减弱4-氨基吡啶(4-AP；250 mU M)和荷包牡丹碱(5-50 mU M)诱发的ACC癫痫样活动，其抑制程度随荷包牡丹碱剂量的不同而不同。刺激丘脑1 Hz可使癫痫样活动减少，而刺激穹隆体能增加癫痫样放电。去掉丘脑输入后，扣带回惊厥样活动的幅度和持续时间均增加，而荷包牡丹碱(50 MU M)升高则无此作用。癫痫样活动始于丘脑II/III层，丘脑损伤后主要发生在V/VI层。二维电流源密度分析显示丘脑损伤后V/VI层汇聚信号更频繁，表明这些层产生更大的兴奋性同步性。在丘脑损伤后，钙瞬变是同步的，这表明ACC癫痫样活动受到丘脑输入的去同步调制。因此，从丘脑内侧传入到深层锥体神经元的去同步化调制使ACC癫痫样活动受控。意义：扣带回癫痫样活动受到丘脑传入的显著调制。反复刺激丘脑有效地抑制了癫痫样活动，表明这种去同步化是路径特异性的。丘脑深部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。
Purpose: 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 thalamicACC slice to clearly determine seizure onset.Methods: We used multielectrode array (MEA) recording and calcium imaging to investigate the modulatory effect of thalamic inputs in a thalamic-ACC slice preparation.Key Findings: Seizure-like activities induced with 4-aminopyridine (4-AP; 250 mu M) and bicuculline (5-50 mu M) 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 mu M). 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.Significance: 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.