Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Elife. 2021 May 21;10:e58779. doi: 10.7554/eLife.58779.
In the postnatal brain, neurogenesis occurs only within a few regions, such as the hippocampal sub-granular zone (SGZ). Postnatal neurogenesis is tightly regulated by factors that balance stem cell renewal with differentiation, and it gives rise to neurons that participate in learning and memory formation. The Kv1.1 channel, a voltage-gated potassium channel, was previously shown to suppress postnatal neurogenesis in the SGZ in a cell-autonomous manner. In this study, we have clarified the physiological and molecular mechanisms underlying Kv1.1-dependent postnatal neurogenesis. First, we discovered that the membrane potential of neural progenitor cells is highly dynamic during development. We further established a multinomial logistic regression model for cell-type classification based on the biophysical characteristics and corresponding cell markers. We found that the loss of Kv1.1 channel activity causes significant depolarization of type 2b neural progenitor cells. This depolarization is associated with increased tropomyosin receptor kinase B (TrkB) signaling and proliferation of neural progenitor cells; suppressing TrkB signaling reduces the extent of postnatal neurogenesis. Thus, our study defines the role of the Kv1.1 potassium channel in regulating the proliferation of postnatal neural progenitor cells in mouse hippocampus.
在出生后的大脑中，神经发生仅发生在几个区域内，例如海马亚颗粒区（SGZ）。出生后的神经发生受到严格的调节，其通过平衡干细胞更新与分化的因素来进行调节，并且产生参与学习和记忆形成的神经元。先前已经表明，电压门控钾通道 Kv1.1 以细胞自主的方式抑制 SGZ 中的出生后神经发生。在这项研究中，我们阐明了 Kv1.1 依赖性出生后神经发生的生理和分子机制。首先，我们发现神经祖细胞的膜电位在发育过程中具有高度动态性。我们进一步建立了基于生物物理特征和相应细胞标记物的细胞类型分类多项逻辑回归模型。我们发现 Kv1.1 通道活性的丧失会导致 2b 型神经祖细胞的明显去极化。这种去极化与原肌球蛋白受体激酶 B（TrkB）信号的增加和神经祖细胞的增殖有关；抑制 TrkB 信号会减少出生后神经发生的程度。因此，我们的研究定义了 Kv1.1 钾通道在调节小鼠海马体中出生后神经祖细胞增殖中的作用。
