Timely Inhibitory Circuit Formation Controlled by Abl1 Regulates Innate Olfactory Behaviors in Mouse

Abstract

Kim et al. reveal that Abl1 is required in early-born olfactory bulb (OB) interneurons during postnatal neurodevelopment. The Abl1-Dcx axis regulates OB circuit formation to support innate olfactory behaviors. The authors propose that Abl1-Dcx is the crucial temporal-specific signal underlying anatomical and/or functional development of postnatal early-born OB interneurons. © 2019 The Author(s)More than one-half of the interneurons in a mouse olfactory bulb (OB) develop during the first week after birth and predominantly connect to excitatory tufted cells near the superficial granule cell layer (sGCL), unlike late-born interneurons. However, the molecular mechanisms underlying the temporal specification are yet to be identified. In this study, we determined the role of Abelson tyrosine-protein kinase 1 (Abl1) in the temporal development of early-born OB interneurons. Lentiviral knockdown of Abl1 disrupts the sGCL circuit of early-born interneurons through defects in function and circuit integration, resulting in olfactory hyper-sensitivity. We show that doublecortin (Dcx) is phosphorylated by Abl1, which contributes to the stabilization of Dcx, thereby regulating microtubule dynamics. Finally, Dcx overexpression rescues Abl1 knockdown-induced anatomic or functional defects. In summary, specific signaling by Abl1-Dcx in early-born interneurons facilitates the temporal development of the sGCL circuit to regulate innate olfactory functions, such as detection and sensitivity. © 2019 The Author(s)