Nassar Mérie, Simonnet Jean, Lofredi Roxanne, Cohen Ivan, Savary Etienne, Yanagawa Yuchio, Miles Richard, Fricker Desdemona
Institut du Cerveau et de la Moelle Epinière, Sorbonne Universités, UPMC Université Paris 06 UM 75, CHU Pitié-Salpêtrière INSERM U1127, CNRS UMR7225 Paris, France.
Neuroscience Paris Seine Paris, Sorbonne Universités, UPMC Université Paris 06 UM CR 18, CNRS UMR 8246, INSERM U1130 Paris, France.
Front Neural Circuits. 2015 May 8;9:20. doi: 10.3389/fncir.2015.00020. eCollection 2015.
The presubiculum, located between hippocampus and entorhinal cortex, plays a fundamental role in representing spatial information, notably head direction. Little is known about GABAergic interneurons of this region. Here, we used three transgenic mouse lines, Pvalb-Cre, Sst-Cre, and X98, to examine distinct interneurons labeled with tdTomato or green fluorescent protein. The distribution of interneurons in presubicular lamina for each animal line was compared to that in the GAD67-GFP knock-in animal line. Labeling was specific in the Pvalb-Cre line with 87% of labeled interneurons immunopositive for parvalbumin (PV). Immunostaining for somatostatin (SOM) revealed good specificity in the X98 line with 89% of fluorescent cells, but a lesser specificity in Sst-Cre animals where only 71% of labeled cells were immunopositive. A minority of ∼6% of interneurons co-expressed PV and SOM in the presubiculum of Sst-Cre animals. The electrophysiological and morphological properties of fluorescent interneurons from Pvalb-Cre, Sst-Cre, and X98 mice differed. Distinct physiological groups of presubicular interneurons were resolved by unsupervised cluster analysis of parameters describing passive properties, firing patterns and AP shapes. One group consisted of SOM-positive, Martinotti type neurons with a low firing threshold (cluster 1). Fast spiking basket cells, mainly from the Pvalb-Cre line, formed a distinct group (cluster 3). Another group (cluster 2) contained interneurons of intermediate electrical properties and basket-cell like morphologies. These labeled neurons were recorded from both Sst-Cre and Pvalb-Cre animals. Thus, our results reveal a wide variation in anatomical and physiological properties for these interneurons, a real overlap of interneurons immuno-positive for both PV and SOM as well as an off-target recombination in the Sst-Cre line, possibly linked to maternal cre inheritance.
前扣带回位于海马体和内嗅皮质之间,在表征空间信息(尤其是头部方向)方面发挥着重要作用。人们对该区域的γ-氨基丁酸能中间神经元知之甚少。在这里,我们使用了三种转基因小鼠品系,即Pvalb-Cre、Sst-Cre和X98,来研究用tdTomato或绿色荧光蛋白标记的不同中间神经元。将每个动物品系前扣带回层中中间神经元的分布与GAD67-GFP敲入动物品系中的分布进行比较。Pvalb-Cre品系的标记具有特异性,87%的标记中间神经元对小白蛋白(PV)免疫阳性。生长抑素(SOM)免疫染色显示X98品系具有良好的特异性,89%的荧光细胞呈阳性,但在Sst-Cre动物中特异性较低,只有71%的标记细胞免疫阳性。在Sst-Cre动物的前扣带回中,约6%的中间神经元共表达PV和SOM。来自Pvalb-Cre、Sst-Cre和X98小鼠的荧光中间神经元的电生理和形态学特性有所不同。通过对描述被动特性、放电模式和动作电位形状的参数进行无监督聚类分析,解析出前扣带回中间神经元的不同生理组。一组由低放电阈值的SOM阳性、马丁诺蒂型神经元组成(第1组)。主要来自Pvalb-Cre品系的快速放电篮状细胞形成一个独特的组(第3组)。另一组(第2组)包含具有中等电学特性和篮状细胞样形态的中间神经元。这些标记神经元是从Sst-Cre和Pvalb-Cre动物中记录到的。因此,我们的结果揭示了这些中间神经元在解剖学和生理学特性上的广泛差异,PV和SOM免疫阳性中间神经元的实际重叠以及Sst-Cre品系中的脱靶重组,这可能与母系cre遗传有关。