Direct pathway neurons in mouse dorsolateral striatum in vivo receive stronger synaptic input than indirect pathway neurons
Direct pathway neurons in mouse dorsolateral striatum in vivo receive stronger synaptic input than indirect pathway neurons
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DOI：
10.1152/jn.00481.2019
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发表时间：
2019-12-01
影响因子：
2.5
通讯作者：
Kumar, Arvind
中科院分区：
文献类型：
--
作者：
Filipovic, Marko;Ketzef, Maya;Kumar, Arvind
纹状体投射神经元是一种中棘神经元，在多种运动和认知功能中起着至关重要的作用。MSN表达D1型或D2型多巴胺受体，分别启动基底节的直接通路(DMSN)和间接通路(IMSN)。DMSN比来自纹状体内来源的iMSN受到更多的抑制。基于这些发现，对鼻孔网络的计算模型预测，在健康条件下，dMSN应该比iMSN获得更多的总输入。为了验证这一预测，我们分析了健康和多巴胺耗竭(60HDA)麻醉小鼠的dMSN和iMSN的体内全细胞记录。通过比较它们的膜电位波动，我们发现dMSN在很宽的频率范围内表现出相当大的膜电位波动。此外，通过比较尖峰触发的平均膜电位。我们发现，dMSN去极化到尖峰阈值的速度明显快于iMSN。总之，这些发现(特别是STA分析)证实了直接通路MSN比间接通路神经元接受更强的总输入的理论预测。最后，我们发现多巴胺耗竭的小鼠的dMSN和iMSN的膜电位波动没有差异。这些数据为多巴胺缺乏如何导致与帕金森病相关的行为缺陷的问题提供了新的见解。值得注意的是，基底神经节的直接和间接通路来自表达D1型和D2型多巴胺受体的中等刺神经元(dMSN和iMSN)。理论结果预测，dMSN应该比iMSN接受更强的突触输入。使用活体细胞内膜电位数据，我们提供了证据，表明dMSN确实比iMSN接收到更强的输入，正如计算模型所预测的那样。
Striatal projection neurons, the medium spiny neurons (MSNs), play a crucial role in various motor and cognitive functions. MSNs express either D1- or D2-type dopamine receptors and initiate the direct-pathway (dMSNs) or indirect pathways (iMSNs) of the basal ganglia, respectively. dMSNs have been shown to receive more inhibition than iMSNs from intrastriatal sources. Based on these findings, computational modeling of the suiatal network has predicted that under healthy conditions dMSNs should receive more total input than iMSNs. To test this prediction, we analyzed in vivo whole cell recordings from dMSNs and iMSNs in healthy and dopamine-depleted (60HDA) anaesthetized mice. By comparing their membrane potential fluctuations, we found that dMSNs exhibited considerably larger membrane potential fluctuations over a wide frequency range. Furthermore, by comparing the spike-triggered average membrane potentials. we found that dMSNs depolarized toward the spike threshold significantly faster than iMSNs did. Together, these findings (in particular the STA analysis) corroborate the theoretical prediction that direct-pathway MSNs receive stronger total input than indirect-pathway neurons. Finally, we found that dopamine-depleted mice exhibited no difference between the membrane potential fluctuations of dMSNs and iMSNs. These data provide new insights into the question of how the lack of dopamine may lead to behavioral deficits associated with Parkinson's disease.NEW & NOTEWORTHY The direct and indirect pathways of the basal ganglia originate from the D1- and D2-type dopamine receptor expressing medium spiny neurons (dMSNs and iMSNs). Theoretical results have predicted that dMSNs should receive stronger synaptic input than iMSNs. Using in vivo intracellular membrane potential data, we provide evidence that dMSNs indeed receive stronger input than iMSNs, as has been predicted by the computational model.