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青春期前雄性和雌性 -tdTomato 线 6 BAC 转基因小鼠纹状体中型多棘神经元亚型的电生理特性。

Electrophysiological Properties of Medium Spiny Neuron Subtypes in the Caudate-Putamen of Prepubertal Male and Female -tdTomato Line 6 BAC Transgenic Mice.

机构信息

Department of Biological Sciences.

W.M. Keck Center for Behavioral Biology.

出版信息

eNeuro. 2019 Mar 13;6(2). doi: 10.1523/ENEURO.0016-19.2019. eCollection 2019 Mar-Apr.

Abstract

The caudate-putamen is a striatal brain region essential for sensorimotor behaviors, habit learning, and other cognitive and premotor functions. The output and predominant neuron of the caudate-putamen is the medium spiny neuron (MSN). MSNs present discrete cellular subtypes that show differences in neurochemistry, dopamine receptor expression, efferent targets, gene expression, functional roles, and most importantly for this study, electrophysiological properties. MSN subtypes include the striatonigral and the striatopallidal groups. Most studies identify the striatopallidal MSN subtype as being more excitable than the striatonigral MSN subtype. However, there is some divergence between studies regarding the exact differences in electrophysiological properties. Furthermore, MSN subtype electrophysiological properties have not been reported disaggregated by biological sex. We addressed these questions using prepubertal male and female Drd1a-tdTomato line 6 BAC transgenic mice, an important transgenic line that has not yet received extensive electrophysiological analysis. We made acute caudate-putamen brain slices and assessed a robust battery of 16 relevant electrophysiological properties using whole-cell patch-clamp recording, including intrinsic membrane, action potential, and miniature EPSC (mEPSC) properties. We found that: (1) MSN subtypes exhibited multiple differential electrophysiological properties in both sexes, including rheobase, action potential threshold and width, input resistance in both the linear and rectified ranges, and mEPSC amplitude; (2) select electrophysiological properties showed interactions between MSN subtype and sex. These findings provide a comprehensive evaluation of mouse caudate-putamen MSN subtype electrophysiological properties across females and males, both confirming and extending previous studies.

摘要

尾状核-壳核是纹状体脑区,对于感觉运动行为、习惯学习和其他认知及运动前功能至关重要。尾状核-壳核的输出和主要神经元是中等棘突神经元(MSN)。MSN 存在离散的细胞亚型,在神经化学、多巴胺受体表达、传出靶标、基因表达、功能作用以及对本研究最重要的电生理特性方面存在差异。MSN 亚型包括纹状体苍白球和纹状体黑质。大多数研究认为纹状体苍白球 MSN 亚型比纹状体黑质 MSN 亚型兴奋性更高。然而,关于电生理特性的确切差异,不同研究之间存在分歧。此外,MSN 亚型的电生理特性尚未按生物性别进行分类报告。我们使用幼年期雄性和雌性 Drd1a-tdTomato 线 6 BAC 转基因小鼠解决了这些问题,这是一种重要的转基因系,尚未进行广泛的电生理分析。我们制备了急性尾状核-壳核脑切片,并使用全细胞膜片钳记录评估了 16 种相关电生理特性的稳健电池,包括固有膜、动作电位和微小 EPSC(mEPSC)特性。我们发现:(1)MSN 亚型在两性中均表现出多种不同的电生理特性,包括基强度、动作电位阈值和宽度、线性和整流范围内的输入电阻以及 mEPSC 幅度;(2)某些电生理特性表现出 MSN 亚型和性别之间的相互作用。这些发现提供了对雌性和雄性小鼠尾状核-壳核 MSN 亚型电生理特性的全面评估,既证实了以前的研究,又扩展了这些研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1401/6426437/611a0f53d097/enu0021928870001.jpg

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