Computational studies of the role of serotonin in the basal ganglia.
Computational studies of the role of serotonin in the basal ganglia.
复制标题
5-羟色胺在基底神经节中的作用的计算研究。
DOI：
10.3389/fnint.2013.00041
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发表时间：
2013
影响因子：
3.5
通讯作者：
Best J
中科院分区：
文献类型：
--
作者：
Reed MC;Nijhout HF;Best J
5-羟色胺（5-HT）在纹状体中起着重要的作用。例如，在帕金森病（PD）的左旋多巴治疗期间，来自中缝背核（DRN）的多巴胺能投射释放多巴胺作为假递质，并且有强烈的迹象表明这种脉动释放与降低治疗有效性的运动障碍有关。在这里，我们提出的假设5-羟色胺在正常纹状体的功能作用，目前的计算研究表明这些假设的可行性。多巴胺能投射到纹状体抑制纹状体帕拉（间接）通路中的中型棘神经元（MSN），并激发纹状体黑质（直接）通路中的MSN。长期以来，人们一直假设，PD中SNc细胞缺失引起的多巴胺（DA）耗竭的作用是改变通路之间的“平衡”，以有利于间接通路。最初，“平衡”被理解为相等的放电率，但现在人们理解DA的水平也会影响两条通路的放电模式。有密集的5-HT从中缝背核投射到纹状体，并且已知纹状体中5-HT的增加促进DA终末的DA释放。直接通路兴奋各种皮质核团，其中一些核团向DRN发送抑制性投射。我们的假设是，这种从纹状体到皮层到DRN再到纹状体的反馈回路用于稳定直接和间接通路之间的平衡，这一点已被我们的模型计算所证实。我们的计算还表明，该回路有助于纹状体中多巴胺浓度的稳定，因为SNc细胞在帕金森病进展期间死亡（直到晚期）。在某些情况下，可能会有生理原因使直接和间接通路“失衡”，我们表明，从皮层或其他大脑区域到DRN的投射可以完成这项任务。
It has been well established that serotonin (5-HT) plays an important role in the striatum. For example, during levodopa therapy for Parkinson's disease (PD), the serotonergic projections from the dorsal raphe nucleus (DRN) release dopamine as a false transmitter, and there are strong indications that this pulsatile release is connected to dyskinesias that reduce the effectiveness of the therapy. Here we present hypotheses about the functional role of 5-HT in the normal striatum and present computational studies showing the feasibility of these hypotheses. Dopaminergic projections to the striatum inhibit the medium spiny neurons (MSN) in the striatopalladal (indirect) pathway and excite MSNs in the striatonigral (direct) pathway. It has long been hypothesized that the effect of dopamine (DA) depletion caused by the loss of SNc cells in PD is to change the “balance” between the pathways to favor the indirect pathway. Originally, “balance” was understood to mean equal firing rates, but now it is understood that the level of DA affects the patterns of firing in the two pathways too. There are dense 5-HT projections to the striatum from the dorsal raphe nucleus and it is known that increased 5-HT in the striatum facilitates DA release from DA terminals. The direct pathway excites various cortical nuclei and some of these nuclei send inhibitory projections to the DRN. Our hypothesis is that this feedback circuit from the striatum to the cortex to the DRN to the striatum serves to stabilize the balance between the direct and indirect pathways, and this is confirmed by our model calculations. Our calculations also show that this circuit contributes to the stability of the dopamine concentration in the striatum as SNc cells die during Parkinson's disease progression (until late phase). There may be situations in which there are physiological reasons to “unbalance” the direct and indirect pathways, and we show that projections to the DRN from the cortex or other brain regions could accomplish this task.