Department of Information Science and Engineering, Ritsumeikan University, Kusatsu, Japan.
Physiol Rep. 2023 Feb;11(4):e15612. doi: 10.14814/phy2.15612.
Parkinson's disease is a movement disorder caused by dopamine depletion in the basal ganglia. Neural activity of the subthalamic nucleus (STN) and globus pallidus externus (GPe) in the basal ganglia are closely related to motor symptoms of Parkinson's disease. However, the pathogenesis of the disease and the transition from the normal state to the pathological state have yet to be elucidated. The functional organization of the GPe is gaining attention due to the recent finding that it consists of two distinct cell populations, namely prototypic GPe neurons and arkypallidal neurons. Identifying connectivity structures between these cell populations, as well as STN neurons, in relation to the dependence of the network activity on the dopaminergic effects is vital. In the present study, using a computational model of the STN-GPe network, we explored biologically plausible connectivity structures between these cell populations. We evaluated the experimentally reported neural activities of these cell types to elucidate the effects of dopaminergic modulation and changes caused by chronic dopamine depletion, such as strengthened connections in the neural activity of the STN-GPe network. Our results indicate that the arkypallidal neurons receive cortical inputs separately from the source for prototypic and STN neurons, suggesting that arkypallidal neurons might be responsible for an additional pathway with the cortex. Furthermore, changes caused by chronic dopamine depletion compensate for the loss of dopaminergic modulation. Changes caused by dopamine depletion itself likely induce the pathological activity observed in patients with Parkinson's disease. However, such changes counteract those of firing rates caused by loss of dopaminergic modulation. In addition, we observed that the STN-GPe tends to exhibit activity with pathological characteristics as side effects.
帕金森病是一种运动障碍疾病，由基底神经节中多巴胺的耗竭引起。基底神经节中的丘脑底核（STN）和苍白球外（GPe）的神经活动与帕金森病的运动症状密切相关。然而，该疾病的发病机制以及从正常状态向病理状态的转变尚未阐明。由于最近发现 GPe 由两种不同的细胞群组成，即原型 GPe 神经元和 arkypallidal 神经元，因此 GPe 的功能组织引起了人们的关注。确定这些细胞群之间的连接结构，以及与网络活动对多巴胺能效应的依赖性相关的 STN 神经元，是至关重要的。在本研究中，我们使用 STN-GPe 网络的计算模型，探索了这些细胞群之间具有生物学意义的连接结构。我们评估了这些细胞类型的实验报告的神经活动，以阐明多巴胺能调制的影响以及慢性多巴胺耗竭引起的变化，例如 STN-GPe 网络的神经活动中增强的连接。我们的结果表明，arkypallidal 神经元从原型和 STN 神经元的来源接收皮质输入，这表明 arkypallidal 神经元可能负责与皮质的另一个通路。此外，慢性多巴胺耗竭引起的变化补偿了多巴胺能调制的丧失。多巴胺耗竭本身引起的变化可能会引起帕金森病患者观察到的病理性活动。然而，这些变化与由于多巴胺能调制丧失引起的放电率变化相抵消。此外，我们观察到 STN-GPe 容易表现出病理性特征的活动作为副作用。
