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研究皮质抑制性 Parvalbumin 表达中间神经元的交叉策略。

Intersectional strategy to study cortical inhibitory parvalbumin-expressing interneurons.

机构信息

Center Anatomy, Institute for Neuroanatomy, University of Göttingen, Göttingen, Germany.

出版信息

Sci Rep. 2024 Feb 3;14(1):2829. doi: 10.1038/s41598-024-52901-y.

DOI:10.1038/s41598-024-52901-y
PMID:38310185
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10838283/
Abstract

Parvalbumin-expressing (PV) interneurons are key neuronal elements to a global excitatory-inhibitory balance in normal cortical functioning. To better understand the circuit functions of PV interneurons, reliable animal models are needed. This study investigated the sensitivity and specificity of the most frequently used PV-Cre/tdTomato mouse line in this regard. The colocalization of the transgene (tdTomato) with the parvalbumin protein, with GAD1 (a conclusive inhibitory cell marker) and Vglut1 (a conclusive excitatory cell marker) as well as with a marker for perineuronal nets (WFA) was assessed and a substantial proportion of layer 5 PV neurons was found to be excitatory and not inhibitory in the PV-Cre/tdTomato mouse. The intersectional transgenic mouse line Vgat-Cre/PV-Flp/tdTomato provided a solution, since no colocalization of tdTomato with the Vglut1 probe was found there. In conclusion, the Vgat-Cre/PV-Flp/tdTomato mouse line seems to be a more reliable animal model for functional studies of GABAergic PV interneurons.

摘要

表达钙结合蛋白 Parvalbumin（PV）的中间神经元是正常皮质功能中整体兴奋-抑制平衡的关键神经元元件。为了更好地理解 PV 中间神经元的回路功能，需要可靠的动物模型。本研究在这方面调查了最常使用的 PV-Cre/tdTomato 小鼠品系的敏感性和特异性。转基因（tdTomato）与 Parvalbumin 蛋白、GAD1（一种结论性的抑制性细胞标记物）和 Vglut1（一种结论性的兴奋性细胞标记物）以及周围神经网（WFA）标记物的共定位情况进行了评估，结果发现 PV-Cre/tdTomato 小鼠的大部分第 5 层 PV 神经元是兴奋性的，而不是抑制性的。Vgat-Cre/PV-Flp/tdTomato 交叉转基因小鼠品系提供了一种解决方案，因为在那里没有发现 tdTomato 与 Vglut1 探针的共定位。总之，Vgat-Cre/PV-Flp/tdTomato 小鼠品系似乎是 GABA 能性 PV 中间神经元功能研究的更可靠的动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/d40347645f03/41598_2024_52901_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/6edced5b4c97/41598_2024_52901_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/2f18827a781c/41598_2024_52901_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/0c5e545aa175/41598_2024_52901_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/ec52307b9ae9/41598_2024_52901_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/f0b13044ceac/41598_2024_52901_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/d40347645f03/41598_2024_52901_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/6edced5b4c97/41598_2024_52901_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/2f18827a781c/41598_2024_52901_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/0c5e545aa175/41598_2024_52901_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/ec52307b9ae9/41598_2024_52901_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/f0b13044ceac/41598_2024_52901_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b224/10838283/d40347645f03/41598_2024_52901_Fig6_HTML.jpg

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