Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
Ming-Yueh Huang
Institute of Statistics, Academia Sinica, Taipei, Taiwan
Chao Chen
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
Yuan-Hung Lin King
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
Grant Guangnan Li
Nkarta Therapeutics Inc, South San Francisco, United States
Wei Zhou
Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States
Chin Fen Teo
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
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States
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.
