Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway
- Academia Sinica, Taiwan
- University of California, San Francisco, United States
- Nkarta Therapeutics Inc, United States
Abstract
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 (Anacker and Hen, 2017; Bond et al., 2015; Toda et al., 2019). 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 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 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 the mouse hippocampus.
Data availability
Most of our results are presented as scatterplots with the intention to show the distribution of our raw data. The variables for the multinomial logistic regression model (fig 5) can be found in the methods section.
Article and author information
Author details
Funding
Ministry of Science and Technology, Taiwan (106-2320-B-001-013)
- Shi-Bing Yang
Ministry of Science and Technology, Taiwan (107-2320-B-001-026-MY3)
- Shi-Bing Yang
NIH Blueprint for Neuroscience Research (R01MH065334)
- Lily Yeh Jan
Howard Hughes Medical Institute (no number)
- Yuh Nung Jan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Moses V Chao, New York University Langone Medical Center, United States
Ethics
Animal experimentation: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and used protocol approved by the Institutional Animal Care and Use Committee of Academia Sinica (protocol#:15-01-813) and the University of California, San Francisco. Mice (3-5 per cage) housed in the animal facility were fed with regular chow diet and subjected to a standard 12-h light/12-h dark cycle. At least 3 animals were used for every single experiment. Mice were first anesthetized with isoflurane followed by decapitation for electrophysiological recordings and immunostaining.
Version history
- Received: May 11, 2020
- Accepted: May 20, 2021
- Accepted Manuscript published: May 21, 2021 (version 1)
- Accepted Manuscript updated: May 26, 2021 (version 2)
- Version of Record published: June 16, 2021 (version 3)
Copyright
© 2021, Chou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway
eLife 10:e58779.
https://doi.org/10.7554/eLife.58779
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