FACS Array Profiling Identifies Ecto-5′ Nucleotidase as a Striatopallidal Neuron-Specific Gene Involved in Striatal-Dependent Learning
FACS Array Profiling Identifies Ecto-5′ Nucleotidase as a Striatopallidal Neuron-Specific Gene Involved in Striatal-Dependent Learning
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DOI：
10.1523/jneurosci.2989-12.2013
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发表时间：
2013-05-15
影响因子：
5.3
通讯作者：
d'Exaerde, Alban de Kerchove
中科院分区：
文献类型：
--
作者：
Ena, Sabrina L.;De Backer, Jean-Francois;d'Exaerde, Alban de Kerchove
纹状核(STP)和纹状体黑质(STN)神经元构成纹状体的主要神经元群。尽管对它们参与与纹状体相关的多个任务的了解越来越多，但了解这两个神经元群体的确切差异功能并识别和研究参与这些功能的新基因仍然是一个挑战。在这里，我们描述了一种可靠的方法，应用于成年小鼠的大脑，以产生特定的STP和STN神经元基因图谱。用转基因Adora2A-Cre x Z/EG小鼠模型结合逆行标记，在同一动物中分别鉴定了STP和STN神经元。从FACS纯化的神经元中产生基因图谱，从而鉴定出新的STP和STN神经元特异性基因。建立了基于Cre依赖慢病毒载体的基因敲除模型，以研究它们在纹状体和STP神经元中的功能。因此，我们证明了胞外-5‘-核苷酸酶(NT5E)在STP神经元中特异表达，并且是纹状体产生的大部分细胞外腺苷的来源。纹状体和STP神经元敲除小鼠模型以及NT5E基因敲除小鼠的行为分析表明，这种STP神经元酶在运动学习中的意义。
The striatopallidal (STP) and striatonigral (STN) neurons constitute the main neuronal populations of the striatum. Despite the increasing knowledge concerning their involvement in multiple tasks associated with the striatum, it is still challenging to understand the precise differential functions of these two neuronal populations and to identify and study new genes involved in these functions. Here, we describe a reliable approach, applied on adult mouse brain, to generate specific STP and STN neuron gene profiles. STP and STN neurons were identified in the same animal using the transgenic Adora2A-Cre x Z/ EG mouse model combined with retrograde labeling, respectively. Gene profiling was generated from FACS-purified neurons leading to the identification of new STP and STN neuron-specific genes. Knock-down models based on Cre-dependent lentiviral vector were developed to investigate their function either in striatal or in STP neurons. Thereby, we demonstrate that ecto-5' -nucleotidase (NT5e) is specifically expressed in STP neurons and is at the origin of most of the extracellular adenosine produced in the striatum. Behavioral analysis of striatal and STP neuron knock-down mouse models as well as NT5e knock-out mice demonstrates the implication of this STP neuron enzyme in motor learning.