Brandon T. Pekarek1,2,3, Mikhail Kochukov3,4, Brittney Lozzi1,2, Timothy Wu1,2,3,5, Patrick J. Hunt1,2,3,5, Burak Tepe2,3, Elizabeth Hanson Moss2,3, Evelyne K. Tantry2,3, Jessica L. Swanson1,2,3, Sean W. Dooling1, Mayuri Patel6,3, Benjamin D.W. Belfort1,2,3,5, Juan M. Romero3,5,7, Suyang Bao6, Matthew C. Hill6 and Benjamin R. Arenkiel2,3,7 1Genetics and Genomics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA; 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; 3Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas 77030, USA; 4Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030, USA; 5Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA; 6Development, Disease Models, and Therapeutics Graduate Program, Baylor College of Medicine, Houston, Texas 77030, USA; 7Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA Corresponding author: arenkielbcm.edu Abstract

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.

Received July 22, 2022. Accepted November 14, 2022.