Abstract—We have analyzed the influence of acetylcholine and GABAergic inhibitory transmission on the functioning of parallel topically organized cortico-basal ganglia–thalamo-cortical neural loops including prefrontal and sensory neocortical areas and the hippocampo-basal ganglia–thalamo–hippocampal loop. Abnormal changes in the acetylcholine concentration as well as in the efficiency of excitation and inhibition in these circuits may lead to various types of epilepsy. Epileptiform activity may develop with the participation of long-range GABAergic cells which promote the synchronization of discharges of excitatory neurons in different structures. We discuss the role of GABAergic interactions between the nuclei of the basal ganglia; GABAergic inputs from hippocampal CA1 field to the medial septum and retrosplenial cortex; from the neocortex to the striatum; and from the external segment of the globus pallidus to the striatum and neocortex. We hypothesized that the limited duration of epileptiform activity is a result of the functioning of several negative feedback loops. These loops are under the influence of GABAergic inputs from the pedunculopontine nucleus to the basal forebrain, thalamus, striatum, basal ganglia outputs, and external segment of the globus pallidus. The influence of acetylcholine is complex because different types of cholinoreceptors are present on excitatory and inhibitory neurons in all structures, and different types of receptors show different affinity for acetylcholine. Our analysis suggests that epileptiform activity may be suppressed by reinforcing the negative feedback loop that is formed by the inhibitory input from the external segment of the globus pallidus to the neocortex. This requires a reduction in the activity of striatal GABAergic spiny cells which project to the neurons of the external segment of the globus pallidus. Since this reduction may be achieved by M1 muscarinic receptor antagonists, they may be used to suppress epileptiform activity. The paper discusses possible side effects of targeting muscarinic receptors in the treatment of various diseases including neurodegenerative disorders. In order to reduce side effects caused by M1 receptor antagonists and other antiepileptic drugs, it is suggested to reduce their dose and use adenosine A2A receptor antagonists. Our conclusions are consistent with the known results of experimental and clinical studies, which means that they may be used in a targeted search for drugs that alleviate the symptoms of various types of epilepsy.

中文翻译：

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乙酰胆碱和GABA能抑制传递在整合新皮层，海马，基底神经节和丘脑的神经网络癫痫发作模式产生中的作用。

摘要—我们分析了乙酰胆碱和GABA抑制性传递对平行局部组织的皮质基底神经节-丘脑-皮质神经环路（包括额叶和感觉新皮质区）和海马基底神经节-丘脑-海马环路的功能的影响。这些回路中乙酰胆碱浓度以及激发和抑制效率的异常变化可能导致各种类型的癫痫病。癫痫样活性可能会随着远程GABA能细胞的参与而发展，这些细胞会促进不同结构中兴奋性神经元放电的同步。我们讨论了基底神经节核之间的GABA能相互作用的作用。从海马CA1场向中隔和脾后皮质的GABA能量输入; 从新皮层到纹状体；从苍白球的外部到纹状体和新皮层。我们假设癫痫样活动的持续时间有限是几个负反馈回路起作用的结果。这些循环受人脚顶足核到基底前脑，丘脑，纹状体，基底神经节输出和苍白球外部的GABA能输入的影响。乙酰胆碱的影响是复杂的，因为在所有结构的兴奋性和抑制性神经元上都存在不同类型的胆碱受体，并且不同类型的受体对乙酰胆碱的亲和力也不同。我们的分析表明，癫痫样活动可以通过加强负反馈回路来抑制，该回路由苍白球的外部段至新皮层的抑制性输入形成。这要求降低投射到苍白球外部部分的神经元的纹状体GABA能棘突细胞的活性。由于这种减少可以通过M1毒蕈碱受体拮抗剂来实现，因此它们可以用于抑制癫痫样活性。该论文讨论了靶向毒蕈碱受体在治疗包括神经退行性疾病在内的各种疾病中可能产生的副作用。为了减少由M1受体拮抗剂和其他抗癫痫药引起的副作用，建议减少其剂量并使用腺苷A2A受体拮抗剂。