Targeted deletion of ERK5 MAP kinase in the developing nervous system impairs development of GABAergic interneurons in the main olfactory bulb and behavioral discrimination between structurally similar odorants

Abstract

ERK5 MAP kinase is highly expressed in the developing nervous system and has been implicated in promoting the survival of immature neuronsinculture. However,itsroleinthedevelopmentandfunctionofthe mammaliannervous system has notbeen establishedin vivo. Here, we report that conditional deletion of the erk5 gene in mouse neural stem cells during development reduces the number of GABAergic interneurons in the main olfactory bulb (OB). Our data suggest that this is due to a decrease in proliferation and an increase inapoptosisinthesubventricularzoneandrostral migratorystreamofERK5 mutantmice.Interestingly, ERK5mutant micehavesmaller OB and are impaired in odor discrimination between structurally similar odorants. We conclude that ERK5 is a novel signaling pathway regulating developmental OB neurogenesis and olfactory behavior. © 2012 the authors.