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Existence and Control of Go/No-Go Decision Transition Threshold in the Striatum

机译:纹状体通过/不通过决策转换阈值的存在与控制

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摘要

A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia. Medium spiny neurons (MSNs) in the striatum, receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine receptors, respectively. Recently, it has become clear that the two types of MSNs markedly differ in their mutual and recurrent connectivities as well as feedforward inhibition from FSIs. Therefore, to understand striatal function in action selection, it is of key importance to identify the role of the distinct connectivities within and between the two types of MSNs on the balance of their activity. Here, we used both a reduced firing rate model and numerical simulations of a spiking network model of the striatum to analyze the dynamic balance of spiking activities in D1 and D2 MSNs. We show that the asymmetric connectivity of the two types of MSNs renders the striatum into a threshold device, indicating the state of cortical input rates and correlations by the relative activity rates of D1 and D2 MSNs. Next, we describe how this striatal threshold can be effectively modulated by the activity of fast spiking interneurons, by the dopamine level, and by the activity of the GPe via pallidostriatal backprojections. We show that multiple mechanisms exist in the basal ganglia for biasing striatal output in favour of either the `Go' or the `No-Go' pathway. This new understanding of striatal network dynamics provides novel insights into the putative role of the striatum in various behavioral deficits in patients with Parkinson's disease, including increased reaction times, L-Dopa-induced dyskinesia, and deep brain stimulation-induced impulsivity.
机译:建议通过激活基底节的直接或间接途径在大脑中执行典型的“通过/不通过”决定。纹状体中的中棘神经元(MSNs)从皮质接受输入并投射到直接和间接途径,分别表达D1和D2型多巴胺受体。近来,已经清楚的是,两种类型的MSN在它们的相互连接和循环连接以及FSI的前馈抑制方面明显不同。因此,要了解纹状体在行动选择中的作用,至关重要的是,要确定两种类型的MSN内部和之间的独特连接在其活动平衡上的作用。在这里,我们使用降低的发射速率模型和纹状体突刺网络模型的数值模拟来分析D1和D2 MSN中突刺活动的动态平衡。我们表明,两种类型的MSN的不对称连通性使纹状体成为阈值设备,通过D1和D2 MSN的相对活动率指示皮质输入速率和相关性的状态。接下来,我们描述如何通过快速突触的中间神经元的活动,多巴胺水平以及通过苍白骨质反投影的GPe活性来有效地调节该纹状体阈值。我们证明了在基底神经节中存在多种机制,它们可以使纹状体输出偏向于“ Go”或“ No-Go”途径。对纹状体网络动力学的这种新理解为纹状体在帕金森氏病患者各种行为缺陷中的假定作用提供了新颖的见解,包括反应时间增加,L-多巴引起的运动障碍和深部脑刺激引起的冲动。

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