Different corticostriatal integration in spiny projection neurons from direct and indirect pathways
Different corticostriatal integration in spiny projection neurons from direct and indirect pathways
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DOI：
10.3389/fnsys.2010.00015
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Galarraga, Elvira
中科院分区：
文献类型：
--
作者：
Flores-Barrera, Eden;Vizcarra-Chacon, Bianca J.;Galarraga, Elvira
纹状体是基底神经节的主要输入结构。纹状体的主要多巴胺能传入来自大脑皮层，并与中型多刺投射神经元（MSN）和中间神经元进行单突触接触。此外：纹状体的多巴胺能传入神经来自丘脑。尽管轴突投射，多巴胺（DA）受体的表达和MSN之间的兴奋性差异从“直接”和“间接”基底神经节通路的差异，这些神经元类已被认为是电生理非常相似。基于对细菌人工染色体（BAC）转基因小鼠的研究，本文显示表达D-1和D-2受体的MSN（D-1-和D-2-MSN）中的皮质纹状体反应是根本不同的，从而建立容易区分它们的电生理足迹。在BAC小鼠中的实验使我们能够以高概率（P > 0.9）预测大鼠或非BAC小鼠中记录的神经元（来自大鼠或小鼠）是否将是P物质或脑啡肽（ENK）免疫反应性的。D-1-MSNs的反应时间更长，诱发更多的动作电位，而D-2-MSNs的反应时间更短，表现出内在的自动再生反应。这些差异的一个主要原因是在每个响应的抑制贡献的内在属性的相互作用。抑制总是压抑皮质纹状体去极化在D-2-MSNs，而它有助于维持长期去极化在D-1-MSNs，尽管压抑早期放电。6-羟基多巴胺（6-OHDA）损伤动物纹状体DA耗竭后皮质纹状体反应发生了显着变化：P物质（SP）+ MSNs反应减少，而ENK+ MSNs反应增强。最终结果是，在DA耗尽后，反应的差异大大减小。
The striatum is the principal input structure of the basal ganglia. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs) and interneurons. Also: glutamatergic afferents to the striatum come from the thalamus. Despite differences in axonal projections, dopamine (DA) receptors expression and differences in excitability between MSNs from "direct"and "indirect"basal ganglia pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with bacterial artificial chromosome (BAC) transgenic mice, here it is shown that corticostriatal responses in D-1-and D-2-receptor expressing MSNs (D-1-and D-2-MSNs) are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P > 0.9), in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin (ENK) immunoreactive. Responses are more prolonged and evoke more action potentials in D-1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D-2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response. Inhibition always depressed corticostriatal depolarization in D-2-MSNs, while it helped in sustaining prolonged depolarizations in D-1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA depletion in 6-hydroxy-dopamine (6-OHDA) lesioned animals: a response reduction was seen in substance P (SP)+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion.