Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3a(EGFP) Mouse.

Novel Striatal GABAergic Interneuron Populations Labeled in the 5HT3a(EGFP) Mouse.
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5HT3a(EGFP) 小鼠中标记的新型纹状体 GABA 能中间神经元群。

DOI:
10.1093/cercor/bhu179
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发表时间:
2016
期刊:
Cerebral cortex (New York, N.Y. : 1991)
影响因子:
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通讯作者:
Hjerling-Leffler,J
Hjerling-Leffler,J
中科院分区:
--
文献类型:
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作者:
Muñoz-Manchado,AB;Foldi,C;Szydlowski,S;Sjulson,L;Farries,M;Wilson,C;Silberberg,G;Hjerling-Leffler,J

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组织学和形态学研究表明,纹状体神经元约5%为胆碱能或γ-氨基丁酸能(GABAergic)中间神经元(gINs)。然而,纹状体神经元表达已知的中间神经元标记的数量太少,不足以说明整个中间神经元群体。因此,我们研究了5 -羟色胺(5HT)受体3a增强的绿色荧光蛋白(5ht3egfp)小鼠,我们发现纹状体中有大量的gINs被标记。大约20%的5ht3egfp阳性细胞共表达小白蛋白,并表现出快速峰(FS)电生理特性。然而,大多数被标记的神经元不与已知的分子间神经元标记重叠。内在电学性质揭示了至少两种不同的新亚型:晚峰值(LS)神经肽- y (NPY)阴性神经胶质样(NGF)中间神经元,以及大量异质群体,具有一些类似低阈值峰值(LTS)中间神经元的特征,不表达生长抑素、NPY或神经元一氧化氮合酶。尽管5HT3aEGFPNGF和lts样中间神经元具有与先前描述的群体相似的电生理特性,但它们在药理学上是不同的。与之前描述的NPY+LTS和NGF细胞形成鲜明对比的是,LTS样5ht3aegfpcell对尼古丁的给药表现出强烈的反应,而5HT3aEGFPNGF细胞类型则表现出很少或没有反应。通过构建这些新种群和现有中间神经元种群之间重叠的分子图谱,我们能够协调纹状体中间神经元数量的形态学和分子估计。
Histological and morphological studies indicate that approximately 5% of striatal neurons are cholinergic or γ-aminobutyric acidergic (GABAergic) interneurons (gINs). However, the number of striatal neurons expressing known interneuron markers is too small to account for the entire interneuron population. We therefore studied the serotonin (5HT) receptor 3a-enhanced green fluorescent protein (5HT3aEGFP) mouse, in which we found that a large number of striatal gINs are labeled. Roughly 20% of 5HT3aEGFP-positive cells co-express parvalbumin and exhibit fast-spiking (FS) electrophysiological properties. However, the majority of labeled neurons do not overlap with known molecular interneuron markers. Intrinsic electrical properties reveal at least 2 distinct novel subtypes: a late-spiking (LS) neuropeptide-Y (NPY)-negative neurogliaform (NGF) interneuron, and a large heterogeneous population with several features resembling low-threshold-spiking (LTS) interneurons that do not express somatostatin, NPY, or neuronal nitric oxide synthase. Although the 5HT3aEGFPNGF and LTS-like interneurons have electrophysiological properties similar to previously described populations, they are pharmacologically distinct. In direct contrast to previously described NPY+LTS and NGF cells, LTS-like 5HT3aEGFPcells show robust responses to nicotine administration, while the 5HT3aEGFPNGF cell type shows little or no response. By constructing a molecular map of the overlap between these novel populations and existing interneuron populations, we are able to reconcile the morphological and molecular estimates of striatal interneuron numbers.