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

• Published in: Cell reports (Cambridge) Vol. 30; no. 1; pp. 187 - 201.e4
• Main Authors: Kim, Jae Yeon, Cho, Bongki, Moon, Cheil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.01.2020; Elsevier
• Subjects: Animals; Animals, Newborn; Behavior, Animal; Enzyme Activation; Female; HEK293 Cells; Humans; Interneurons - physiology; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Neural Inhibition; Neurites - metabolism; Neurogenesis; Neuropeptides - metabolism; Olfactory Bulb - growth & development; Phosphorylation; Protein Stability; Proto-Oncogene Proteins c-abl - metabolism; Smell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.12.004

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. [Display omitted] •Abl1 governs development of postnatal early-born olfactory bulb (OB) interneurons•Abl1 is required for building the OB circuit that controls olfactory sensitivity•Abl1-Dcx signaling drives structural changes in interneurons•Abl1 and Dcx coordinate to promote development of innate olfactory behaviors 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.