Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways
Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways
复制标题
DOI：
10.1523/jneurosci.4646-13.2014
复制
发表时间：
2014-02-05
影响因子：
5.3
通讯作者：
Gittis, Aryn H.
中科院分区：
文献类型：
--
作者：
Mastro, Kevin J.;Bouchard, Rachel S.;Gittis, Aryn H.
大脑中细胞类型的多样性使复杂的神经回路得以组装，其组织和活动模式引发了大脑功能。然而，由于缺乏客观的标准来区分不同的神经元群体，在给定的大脑区域内识别不同的神经元群体往往是复杂的。在苍白球(GPE)的外段，已经使用分子、解剖学和电生理学标准来定义神经元群体，但这些分类方案通常不能在不同的制备方法中推广，即使在相同的制备方法中也缺乏一致性。在这里，我们提出了一种新的使用现有的转基因小鼠系LIM Homeobox 6(Lhx6)-Cre和小白蛋白(PV)-Cre来定义GPE中在分子、解剖和电生理上不同的遗传不同细胞群。Lhx6-GPE神经元不表达PV，集中在GPE的内侧部。与PV-GPE神经元相比，它们的自发放电频率更低，动态范围更窄，向纹状体和黑质致密部的投射更强。相反，PV-GPE神经元更集中在GPE的外侧部分。它们具有更窄的动作电位，更深的后超极化，并向丘脑底核和丘脑束旁核发出更强的投射。这些电生理和解剖学差异表明，Lhx6-GPE和PV-GPE神经元参与不同的回路，可能参与疾病中运动功能和功能障碍的不同方面。
Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)-Cre and parvalbumin (PV)-Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6-GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV-GPe neurons. In contrast, PV-GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6-GPe and PV-GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease.