Patterned endogenous activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb

Li, K.; Figarella, K.; Su, X.; Kovalchuk, Y.; Gorzolka, J.; Neher, J.; Mojtahedi, N.; Casadei, N.; Hedrich-Klimosch, U.; Garaschuk, O.

doi:10.1101/2021.04.21.440775

bioRxiv · 10.1101/2021.04.21.440775

Patterned endogenous activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb

Li, K.·Figarella, K.·Su, X.·Kovalchuk, Y.·Gorzolka, J.·Neher, J.·Mojtahedi, N.·Casadei, N.·Hedrich-Klimosch, U.·Garaschuk, O.

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Abstract

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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Li, K., Figarella, K., Su, X., Kovalchuk, Y., Gorzolka, J., Neher, J., Mojtahedi, N., Casadei, N., Hedrich-Klimosch, U., Garaschuk, O.. 2021-04-22. Patterned endogenous activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb. https://doi.org/10.1101/2021.04.21.440775

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