Endogenous but Not Sensory-Driven Activity Controls Migration, Morphogenesis and Survival of Adult-Born Juxtaglomerular Neurons in the Mouse Olfactory Bulb

Authors

Kaizhen Li
Katherine Figarella
Xin Su
Yury Kovalchuk
Jessika Gorzolka
Jonas J Neher
Nima Mojtahedi
Nicolas Casadei
Ulrike B S Hedrich
Olga Garaschuk

Publication Date

3-18-2023

Journal

Cellular and Molecular Life Sciences

Abstract

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.

Keywords

Mice, Animals, Olfactory Bulb, Neurons, Neurogenesis, Cell Differentiation, Cell Movement