Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, 1094, Hungary.
ELRN Institute of Experimental Medicine, Budapest, 1083, Hungary.
J Neurosci. 2021 May 26;41(21):4575-4595. doi: 10.1523/JNEUROSCI.2700-20.2021. Epub 2021 Apr 9.
GABAergic neurons are key circuit elements in cortical networks. Despite growing evidence showing that inhibitory cells play a critical role in the lateral (LA) and basal (BA) amygdala functions, neither the number of GABAergic neurons nor the ratio of their distinct types has been determined in these amygdalar nuclei. Using unbiased stereology, we found that the ratio of GABAergic neurons in the BA (22%) is significantly higher than in the LA (16%) in both male and female mice. No difference was observed between the right and left hemispheres in either sex. In addition, we assessed the ratio of the major inhibitory cell types in both amygdalar nuclei. Using transgenic mice and a viral strategy for visualizing inhibitory cells combined with immunocytochemistry, we estimated that the following cell types together compose the vast majority of GABAergic cells in the LA and BA: axo-axonic cells (5.5%-6%), basket cells expressing parvalbumin (17%-20%) or cholecystokinin (7%-9%), dendrite-targeting inhibitory cells expressing somatostatin (10%-16%), NPY-containing neurogliaform cells (14%-15%), VIP and/or calretinin-expressing interneuron-selective interneurons (29%-38%), and GABAergic projection neurons expressing somatostatin and neuronal nitric oxide synthase (5.5%-8%). Our results show that these amygdalar nuclei contain all major GABAergic neuron types as found in other cortical regions. Furthermore, our data offer an essential reference for future studies aiming to reveal changes in GABAergic cell number and in inhibitory cell types typically observed under different pathologic conditions, and to model functioning amygdalar networks in health and disease. GABAergic cells in cortical structures, as in the lateral and basal nucleus of the amygdala, have a determinant role in controlling circuit operation. In this study, we provide the first estimate for the total number of inhibitory cells in these two amygdalar nuclei. In addition, our study is the first to define the ratio of the major GABAergic cell types present in these cortical networks. Taking into account that hyperexcitability in the amygdala, arising from the imbalance between excitation and inhibition typifies many altered brain functions, including anxiety, post-traumatic stress disorder, schizophrenia, and autism, uncovering the number and ratio of distinct amygdalar inhibitory cell types offers a solid base for comparing the changes in inhibition in pathologic brain states.
GABA 能神经元是皮质网络中的关键回路元件。尽管越来越多的证据表明抑制性细胞在外侧(LA)和基底(BA)杏仁核功能中起着关键作用,但在这些杏仁核核中尚未确定 GABA 能神经元的数量及其不同类型的比例。使用无偏立体学,我们发现雄性和雌性小鼠 BA(22%)中的 GABA 能神经元比例明显高于 LA(16%)。在两性中,左右半球之间没有差异。此外,我们评估了两个杏仁核核中主要抑制性细胞类型的比例。使用转基因小鼠和一种用于可视化抑制性细胞的病毒策略,结合免疫细胞化学,我们估计以下细胞类型共同构成了 LA 和 BA 中绝大多数 GABA 能细胞:轴突-轴突细胞(5.5%-6%),表达囊泡蛋白(PV)的篮状细胞(17%-20%)或胆囊收缩素(CCK)(7%-9%),靶向树突的抑制性细胞表达生长抑素(SST)(10%-16%),含有 NPY 的神经胶质形成细胞(NPY-GF)(14%-15%),VIP 和/或钙视网膜蛋白表达的神经元选择性中间神经元(29%-38%),和表达生长抑素和神经元一氧化氮合酶(SOM 和 nNOS)的 GABA 能投射神经元(5.5%-8%)。我们的结果表明,这些杏仁核核包含了在其他皮质区域中发现的所有主要 GABA 能神经元类型。此外,我们的数据为未来的研究提供了重要的参考,这些研究旨在揭示在不同病理条件下 GABA 能细胞数量和抑制性细胞类型的变化,并在健康和疾病中模拟杏仁核网络的功能。皮质结构中的 GABA 能细胞,如外侧和基底杏仁核核,在控制回路运作方面具有决定性作用。在这项研究中,我们首次对这两个杏仁核核中抑制性细胞的总数进行了估计。此外,我们的研究首次定义了这些皮质网络中存在的主要 GABA 能细胞类型的比例。考虑到杏仁核的过度兴奋,这种兴奋源于兴奋与抑制之间的不平衡,是许多改变大脑功能的特征,包括焦虑、创伤后应激障碍、精神分裂症和自闭症,揭示不同杏仁核抑制性细胞类型的数量和比例为比较病理性大脑状态下抑制的变化提供了坚实的基础。