期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 80, 期 4, 页码 -出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-023-04753-4
关键词
Adult neurogenesis; Potassium channels; Olfactory bulb; Neuronal development; Endogenous activity; Spontaneous calcium transients; pCREB; Migration; Differentiation; Survival
The development and survival of adult-born neurons are dependent on sensory signaling. Through in vivo analyses, it was found that impairments in migration, morphogenesis, survival, and functional integration were observed in adult-born juxtaglomerular cells with reduced excitability. Overexpression of Kv1.2 or Kir2.1 K+ channels led to downregulation of genes involved in neuronal migration and differentiation, and upregulation of apoptosis-related genes. Surprisingly, cells deprived of sensory-driven activity developed normally.
The development and survival of adult-born neurons are believed to be driven by sensory signaling. Here, in vivo analyses of motility, morphology and Ca2+ signaling, as well as transcriptome analyses of adult-born juxtaglomerular cells with reduced endogenous excitability (via cell-specific overexpression of either Kv1.2 or Kir2.1 K+ channels), revealed a pronounced impairment of migration, morphogenesis, survival, and functional integration of these cells into the mouse olfactory bulb, accompanied by a reduction in cytosolic Ca2+ fluctuations, phosphorylation of CREB and pCREB-mediated gene expression. Moreover, K+ channel overexpression strongly downregulated genes involved in neuronal migration, differentiation, and morphogenesis and upregulated apoptosis-related genes, thus locking adult-born cells in an immature and vulnerable state. Surprisingly, cells deprived of sensory-driven activity developed normally. Together, the data reveal signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+ fluctuations as well as enhanced Kv1.2/Kir2.1 K+ channel function to migration, maturation, and survival of adult-born neurons.
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