ABSTRACT
3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.
ABSTRACT
The hypothalamic neuropeptide, oxytocin (Oxt), has been the focus of research for decades due to its effects on body physiology, neural circuits, and various behaviors. Oxt elicits a multitude of actions mainly through its receptor, the Oxt receptor (OxtR). Despite past research to understand the central projections of Oxt neurons and OxtR- coupled signaling pathways in different brain areas, it remains unclear how this nonapeptide exhibits such pleiotropic effects while integrating external and internal information. Most reviews in the field either focus on neuroanatomy of the Oxt-OxtR system, or on the functional effects of Oxt in specific brain areas. Here, we provide a review by integrating brain wide connectivity of Oxt neurons and their downstream circuits with OxtR expression in mice. We categorize Oxt connected brain regions into three functional modules that regulate the internal state, somatic visceral, and cognitive response. Each module contains three neural circuits that process distinct behavioral effects. Broad innervations on functional circuits (e.g., basal ganglia for motor behavior) enable Oxt signaling to exert coordinated modulation in functionally inter-connected circuits. Moreover, Oxt acts as a neuromodulator of neuromodulations to broadly control the overall state of the brain. Lastly, we discuss the mismatch between Oxt projections and OxtR expression across various regions of the mouse brain. In summary, this review brings forth functional circuit-based analysis of Oxt connectivity across the whole brain in light of Oxt release and OxtR expression and provides a perspective guide to future studies.
