Bidirectional control of absence seizures by the basal ganglia: a computational evidence.
Bidirectional control of absence seizures by the basal ganglia: a computational evidence.
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基底神经节对失神发作的双向控制：计算证据
DOI：
10.1371/journal.pcbi.1003495
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发表时间：
2014-03
影响因子：
4.3
通讯作者：
Yao D
中科院分区：
文献类型：
--
作者：
Chen M;Guo D;Wang T;Jing W;Xia Y;Xu P;Luo C;Valdes-Sosa PA;Yao D
失神癫痫被认为与大脑皮层和丘脑之间的异常相互作用有关。解剖学证据表明，大脑皮层和丘脑之间除了直接联系外，还通过一个重要的中间桥梁--基底神经节进行间接联系。基底神经节可能在失神发作的调制中起关键作用，但相关的生物物理机制尚未完全建立。利用生物物理学模型，我们证明了典型的失神发作活动可以通过从黑质网状部（SNr）到丘脑网状核（TRN）或丘脑特定中继核（SRN）的直接GABA能投射，通过不同的生物物理机制来控制和调节。在某些条件下，这两种类型的缉获控制被观察到在同一网络中共存。更重要的是，由于抑制SNr-TRN和SNr-SRN通路之间的竞争，我们发现，无论是从正常水平上减少或增加SNr神经元的激活可能会大大抑制在共存区的棘波和慢波放电的产生。总之，这些结果突出了基底神经节在控制和调节失神发作中的双向功能作用，并可能为这种脑疾病的治疗提供新的见解。癫痫是一种常见的癫痫病。失神发作是癫痫发作的一种，其特征是典型的2-4 Hz棘慢波放电（SWDs）。越来越多的证据表明，失神发作是由于大脑皮质和丘脑之间的异常相互作用造成的，基底神经节可能通过在上级丘中继的间接基底神经节-丘脑通路参与控制此类脑部疾病。实际上，基底节不仅向丘脑发出间接信号，而且还通过多种直接的GABA能投射与丘脑的几个关键核团进行联系。然而，这些直接通路是否以及如何调节失神发作活动仍然是未知的。通过计算机模拟，我们预测，两个直接抑制性基底神经节丘脑通路发射的黑质网状部也可能参与控制失神发作。此外，我们发现，这两种类型的癫痫发作控制可以共存于同一个网络，并根据即时的网络状态，无论是降低和增加SNr神经元的激活可能会抑制SWDs由于竞争的存在。我们的研究结果强调了基底神经节对失神发作的双向调节作用，并可能对失神癫痫的治疗具有生理意义。
Absence epilepsy is believed to be associated with the abnormal interactions between the cerebral cortex and thalamus. Besides the direct coupling, anatomical evidence indicates that the cerebral cortex and thalamus also communicate indirectly through an important intermediate bridge–basal ganglia. It has been thus postulated that the basal ganglia might play key roles in the modulation of absence seizures, but the relevant biophysical mechanisms are still not completely established. Using a biophysically based model, we demonstrate here that the typical absence seizure activities can be controlled and modulated by the direct GABAergic projections from the substantia nigra pars reticulata (SNr) to either the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of thalamus, through different biophysical mechanisms. Under certain conditions, these two types of seizure control are observed to coexist in the same network. More importantly, due to the competition between the inhibitory SNr-TRN and SNr-SRN pathways, we find that both decreasing and increasing the activation of SNr neurons from the normal level may considerably suppress the generation of spike-and-slow wave discharges in the coexistence region. Overall, these results highlight the bidirectional functional roles of basal ganglia in controlling and modulating absence seizures, and might provide novel insights into the therapeutic treatments of this brain disorder. Epilepsy is a general term for conditions with recurring seizures. Absence seizures are one of several kinds of seizures, which are characterized by typical 2–4 Hz spike-and-slow wave discharges (SWDs). There is accumulating evidence that absence seizures are due to abnormal interactions between cerebral cortex and thalamus, and the basal ganglia may take part in controlling such brain disease via the indirect basal ganglia-thalamic pathway relaying at superior colliculus. Actually, the basal ganglia not only send indirect signals to thalamus, but also communicate with several key nuclei of thalamus through multiple direct GABAergic projections. Nevertheless, whether and how these direct pathways regulate absence seizure activities are still remain unknown. By computational modelling, we predicted that two direct inhibitory basal ganglia-thalamic pathways emitting from the substantia nigra pars reticulata may also participate in the control of absence seizures. Furthermore, we showed that these two types of seizure control can coexist in the same network, and depending on the instant network state, both lowing and increasing the activation of SNr neurons may inhibit the SWDs due to the existence of competition. Our findings emphasize the bidirectional modulation effects of basal ganglia on absence seizures, and might have physiological implications on the treatment of absence epilepsy.
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影响因子：
3.1
作者：
Groenewegen HJ
通讯作者：
Groenewegen HJ
影响因子：
3.8
作者：
Gulcebi, Medine Idrizoglu;Ketenci, Sema;Cavdar, Safiye
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具有不可靠突触的前馈神经元网络中的信号传播
影响因子：
1.2
作者：
Guo, Daqing;Li, Chunguang
通讯作者：
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作者：
da Silva, FL;Blanes, W;Velis, DN
通讯作者：
Velis, DN
影响因子：
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作者：
Breakspear, M.;Roberts, J. A.;Robinson, P. A.
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Robinson, P. A.