Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway

eLife

Wei Zhou¹  Lily Yeh Jan²  Chin Fen Teo²  Chao Chen²  Yuh Nung Jan²  Ke-Xin Li²  Yuan-Hung Lin King³  Shu-Min Chou⁴  Shi-Bing Yang⁵  Ming-Yueh Huang⁶  Grant Guangnan Li⁷ 

[1] Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States;Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States;Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States;Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;Neuroscience Program of Academia Sinica, Academia Sinica, Taipei, Taiwan;Institute of Statistics, Academia Sinica, Taipei, Taiwan;Nkarta Therapeutics Inc, South San Francisco, United States;

关键词: postnatal neurogenesis;    voltage-gated potassium channel;    neural progenitor cells;    Mouse;   

DOI  :  10.7554/eLife.58779

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY