期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：22
DOI：10.1073/pnas.2118240119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Despite decades of research on adult neurogenesis, little is known about the role of bioelectric signaling in this process. In this study, we describe how a voltage-gated potassium channel, K
v1.1, supports adult neurogenesis by maintaining the neural stem cell niche and facilitating newborn neuron development. Additionally, we show that deletion of K
v1.1 from adult neural stem cells contributes to modest impairments in hippocampus-dependent contextual fear learning and memory. Dysfunctional adult neurogenesis has been implicated in cognitive decline associated with aging and neurological disease. Therefore, understanding the role of K
v1.1 in adult neurogenesis represents an opportunity to identify new therapeutic targets to promote healthy neurogenesis and cognition.
Adult hippocampal neurogenesis is critical for learning and memory, and aberrant adult neurogenesis has been implicated in cognitive decline associated with aging and neurological diseases [J. T. Gonçalves, S. T. Schafer, F. H. Gage,
Cell 167, 897–914 (2016)]. In previous studies, we observed that the delayed-rectifier voltage-gated potassium channel K
v1.1 controls the membrane potential of neural stem and progenitor cells and acts as a brake on neurogenesis during neonatal hippocampal development [S. M. Chou
et al.,
eLife 10, e58779 (2021)]. To assess the role of K
v1.1 in adult hippocampal neurogenesis, we developed an inducible conditional knockout mouse to specifically remove K
v1.1 from adult neural stem cells via tamoxifen administration. We determined that K
v1.1 deletion in adult neural stem cells causes overproliferation and depletion of radial glia-like neural stem cells, prevents proper adult-born granule cell maturation and integration into the dentate gyrus, and moderately impairs hippocampus-dependent contextual fear learning and memory. Taken together, these findings support a critical role for this voltage-gated ion channel in adult neurogenesis.
关键词：envoltage-gated potassium channeladult neurogenesishippocampuslearning and memory
