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.

Cellular senescence is a highly complicated cellular state that occurs throughout the lifespan of an organism. It has been well-defined in mitotic cells by various senescent features. Neurons are long-lived postmitotic cells with special structures and functions. With age, neurons display morphological and functional changes, accompanying alterations in proteostasis, redox balance, and Ca 2+ dynamics; however, it is ambiguous whether these neuronal changes belong to the features of neuronal senescence. In this review, we strive to identify and classify changes that are relatively specific to neurons in the aging brain and define them as features of neuronal senescence through comparisons with common senescent features. We also associate them with the functional decline of multiple cellular homeostasis systems, proposing the possibility that these systems are the main drivers of neuronal senescence. We hope this summary will serve as a steppingstone for further inputs on a comprehensive but relatively specific list of phenotypes for neuronal senescence and in particular their underlying molecular events during aging. This will in turn shine light on the association between neuronal senescence and neurodegeneration and lead to the development of strategies to perturb the processes.

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