The University of Queensland, Queensland Brain Institute, Brisbane, QLD, Australia.
Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.
Mol Psychiatry. 2018 Mar;23(3):521-532. doi: 10.1038/mp.2017.134. Epub 2017 Aug 15.
New neurons are continually generated from the resident populations of precursor cells in selective niches of the adult mammalian brain such as the hippocampal dentate gyrus and the olfactory bulb. However, whether such cells are present in the adult amygdala, and their neurogenic capacity, is not known. Using the neurosphere assay, we demonstrate that a small number of precursor cells, the majority of which express Achaete-scute complex homolog 1 (Ascl1), are present in the basolateral amygdala (BLA) of the adult mouse. Using neuron-specific Thy1-YFP transgenic mice, we show that YFP+ cells in BLA-derived neurospheres have a neuronal morphology, co-express the neuronal marker βIII-tubulin, and generate action potentials, confirming their neuronal phenotype. In vivo, we demonstrate the presence of newly generated BrdU-labeled cells in the adult BLA, and show that a proportion of these cells co-express the immature neuronal marker doublecortin (DCX). Furthermore, we reveal that a significant proportion of GFP+ neurons (~23%) in the BLA are newly generated (BrdU+) in DCX-GFP mice, and using whole-cell recordings in acute slices we demonstrate that the GFP+ cells display electrophysiological properties that are characteristic of interneurons. Using retrovirus-GFP labeling as well as the Ascl1 mouse line, we further confirm that the precursor cells within the BLA give rise to mature and functional interneurons that persist in the BLA for at least 8 weeks after their birth. Contextual fear conditioning has no effect on the number of neurospheres or BrdU-labeled cells in the BLA, but produces an increase in hippocampal cell proliferation. These results demonstrate that neurogenic precursor cells are present in the adult BLA, and generate functional interneurons, but also show that their activity is not regulated by an amygdala-dependent learning paradigm.
新的神经元不断从成年哺乳动物大脑中的特定部位的祖细胞中产生，如海马齿状回和嗅球。然而，成年杏仁核中是否存在这样的细胞，以及它们的神经发生能力，目前尚不清楚。我们使用神经球测定法证明，少量的祖细胞存在于成年小鼠的基底外侧杏仁核（BLA）中，其中大多数表达 Achaete-scute 复合物同源物 1（Ascl1）。我们利用神经元特异性 Thy1-YFP 转基因小鼠，证明 BLA 衍生的神经球中的 YFP+细胞具有神经元形态，共同表达神经元标志物 βIII-tubulin，并产生动作电位，证实了它们的神经元表型。在体内，我们证明了成年 BLA 中有新产生的 BrdU 标记细胞的存在，并表明这些细胞中有一部分共同表达未成熟神经元标志物双皮质素（DCX）。此外，我们发现 GFP+神经元中有相当一部分（~23%）在 DCX-GFP 小鼠中是新产生的（BrdU+），并且使用急性切片中的全细胞膜片钳记录证明，这些 GFP+细胞显示出特征性的中间神经元电生理特性。通过使用逆转录病毒-GFP 标记以及 Ascl1 小鼠系，我们进一步证实 BLA 中的祖细胞产生成熟和功能正常的中间神经元，这些中间神经元在出生后至少 8 周内仍存在于 BLA 中。情景恐惧条件作用对 BLA 中的神经球或 BrdU 标记细胞的数量没有影响，但会增加海马细胞的增殖。这些结果表明，神经发生前体细胞存在于成年 BLA 中，并产生功能性的中间神经元，但也表明它们的活性不受杏仁核依赖的学习范式的调节。
