Kv1.1 preserves the neural stem cell pool and facilitates neuron maturation during adult hippocampal neurogenesis

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. Goncalves, 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(v)1.1 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(v)1.1 in adult hippocampal neurogenesis, we developed an inducible conditional knockout mouse to specifically remove K(v)1.1 from adult neural stem cells via tamoxifen administration. We determined that K(v)1.1 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.

Automated summary

Adult hippocampal neurogenesis plays a critical role in learning and memory, and the K(v)1.1 channel has been identified as an important regulator in this process. Deletion of K(v)1.1 leads to overproliferation and depletion of adult neural stem cells, impairs maturation and integration of new cells in the hippocampus, and moderately affects hippocampus-dependent contextual fear learning and memory.