Endogenous but not sensory-driven activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb
2021
The development and survival of adult-born neurons is believed to be driven by sensory
signaling. By genetically manipulating excitability of adult-born cells (via cell-specific
overexpression of either Kv1.2 or Kir2.1 K+ channels), longitudinal in vivo monitoring of
their Ca2+ signaling and transcriptome analyses, we show that endogenous but not
sensory-driven activity governs migration, morphogenesis, survival, and functional
integration of adult-born juxtaglomerular neurons in the mouse olfactory bulb. The proper
development of these cells required fluctuations of cytosolic Ca2+ levels, phosphorylation
of CREB, and pCREB-mediated gene expression. Attenuating Ca2+ fluctuations via K+
channel overexpression strongly downregulated genes involved in neuronal migration,
differentiation, and morphogenesis and upregulated apoptosis-related genes, thus
locking adult-born cells in the vulnerable and immature state. Together, the data reveal
signaling pathways connecting the endogenous intermittent neuronal activity/Ca2+
fluctuations as well as proper Kv1.2/Kir2.1 K+ channel function to migration, maturation,
and survival of adult-born neurons.
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