Quantitative Cellular-Resolution Map of the Oxytocin Receptor in Postnatally Developing Mouse Brains

Newmaster, Kyra T.; Nolan, Zachary T.; Chon, Uree; Vanselow, Daniel J.; Weit, Abigael R.; Tabbaa, Manal; Hidema, Shizu; Nishimori, Katsuhiko; Hammock, Elizabeth A. D.; Kim, Yongsoo

doi:10.1101/719229

Cited by 17 publications

(35 citation statements)

References 65 publications

(99 reference statements)

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“…Previous studies suggested a mismatch between presynaptic OT projection and postsynaptic OTR expression (3,34), yet quantitative brain-wide comparison has not been conducted. Previously, we validated that OTR-Venus mice represent the endogenous OTR expression faithfully (11). We imaged a cohort of adult OTR-Venus mice using serial twophoton tomography and mapped OTR expression in the whole adult brain (n=14, green in Table S3. 4A).…”

Section: Comparison Of Oxytocin Output and Oxytocin Receptor Expressionmentioning

confidence: 98%

“…The rest of the OT neurons are expressed in 10 different brain regions (Table S1). The Cre-driven reporter system used in the present study permanently labels all Cre positive cells including developmentally transient expression (11). To distinguish neurons actively expressing OT in adult from developmentally labeled cells, we performed immunohistochemistry using an OT antibody in OT:Ai14 mice.…”

Section: Quantitative Expression Of Oxytocin Neurons In the Mouse Brainmentioning

confidence: 99%

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Whole brain wiring diagram of oxytocin system in adult mice

Son

Manjila

Newmaster

et al. 2020

Preprint

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In the brain, oxytocin (OT) neurons make direct connections with discreet regions to regulate social behavior and diverse physiological responses. Obtaining an integrated neuroanatomical understanding of pleiotropic OT functions requires comprehensive wiring diagram of OT neurons. Here, we have created a whole-brain map of distribution and anatomical connections of hypothalamic OT neurons, and their relationship with OT receptor (OTR) expression. We used our brain-wide quantitative mapping at cellular resolution combined with a 2D flatmap to provide an intuitive understanding of the spatial arrangements of OT neurons. Then, we utilized knock-in Ot-Cre mice injected with Cre dependent retrograde monosynaptic rabies viruses and anterograde adeno associated virus to interrogate input-output patterns. We find that brain regions with cognitive functions such as the thalamus are reciprocally connected, while areas associated with physiological functions such as the hindbrain receive unidirectional outputs. Lastly, comparison between OT output and OTR expression showed no significant quantitative correlation, suggesting that OT transmission mostly occurs through indirect pathways. In summary, our OT wiring diagram provides structural and quantitative insights of distinct behavioral functions of OT neurons in the brain.

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Section: Comparison Of Oxytocin Output and Oxytocin Receptor Expressionmentioning

confidence: 98%

Section: Quantitative Expression Of Oxytocin Neurons In the Mouse Brainmentioning

confidence: 99%

Whole brain wiring diagram of oxytocin system in adult mice

Son

Manjila

Newmaster

et al. 2020

Preprint

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“…Serial two photon tomography (STPT) imaging. Prior to imaging, the brain sample was embedded in oxidized agarose and cross-linked in 0.05M sodium borohydrate at 4C for at least 2 days ahead of imaging (Kim et al, 2017;Newmaster et al, 2019). This procedure allows for seamless cutting at 50μm thick sections, while also preventing any tearing of the brain surface.…”

Section: Animalsmentioning

confidence: 99%

“…Signals in the green and red spectrum were simultaneously collected using a 560 nm dichroic mirror (Chroma). For pericyte and neuronal subtypes, STPT imaging was conducted with 1x1 μm (x,y) resolution in every 50 μm (z), with the imaging plane set at 40μm deep from the surface, as previously described (Kim et al, 2017;Newmaster et al, 2019). For vascular imaging, optical imaging (5 μm z step, 10 steps to cover 50μm in z) was added in the imaging, producing 1x1x5 μm (x,y,z) resolution beginning at 20μm deep from the surface.…”

Section: Animalsmentioning

confidence: 99%

The cellular architecture of microvessels, pericytes and neuronal cell types in organizing regional brain energy homeostasis in mice

Chon

et al. 2021

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The cerebrovascular network and its mural cells must meet the dynamic energy demands of different neuronal cell types across the brain, but their spatial relationship among these cells is largely unknown. Here, we apply brain-wide mapping methods to create a comprehensive cellular-resolution resource comprising the distribution of and quantitative relationship between microvessels, pericytes, and glutamatergic and GABAergic neurons including neuronal nitric oxide synthase-positive (nNOS+) neurons and their subtypes in mice. Leveraging these data, we discovered region-specific signatures of vasculature and cell type compositions across cortical and subcortical areas, including strikingly contrasting correlations between the density of vasculature, pericytes, glutamatergic neurons and parvalbumin-positive interneurons versus nNOS+ neurons in the isocortex. We also found surprisingly low vasculature and pericyte density in the hippocampus, and distinctly high pericyte to vasculature ratio in the hypothalamus. These findings suggest that vascular density and mural cell composition is finely tuned to maintain regional energy homeostasis.

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“…These brains were stored in 0.05M phosphate buffer (PB) at 4°C until imaging. Detailed information about STPT imaging and analysis were previously described (Jeong et al, 2016;Newmaster et al, 2020). Briefly, the brain samples were embedded in oxidized 4% agarose and cross-linked by 0.05M sodium borohydride for imaging preparation.…”

Section: Stpt Imaging and Data Analysismentioning

confidence: 99%

Topographically Distinct Projection Patterns of Early-Generated and Late-Generated Projection Neurons in the Mouse Olfactory Bulb

Chon

LaFever

Nguyen

et al. 2020

eNeuro

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In the mouse brain, olfactory information is transmitted to the olfactory cortex via olfactory bulb (OB) projection neurons known as mitral and tufted cells. Although mitral and tufted cells share many cellular characteristics, these cell types are distinct in their somata location and in their axonal and dendritic projection patterns. Moreover, mitral cells consist of heterogeneous subpopulations. We have previously shown that mitral cells generated at different embryonic days differentially localize within the mitral cell layer and extend their lateral dendrites to different sublayers of the external plexiform layer. Here, we examined the axonal projection patterns from the subpopulations of OB projection neurons that are determined by the timing of neurogenesis (neuronal birthdate) to understand the developmental origin of the diversity in olfactory pathways. We separately labeled early-and late-generated OB projection neurons using in utero electroporation performed at embryonic day 11 and 12, respectively, and quantitatively analyzed their axonal projection patterns in the whole mouse brain using highresolution 3D imaging. In this study, we demonstrate that the axonal projection of late-generated OB projection neurons is restricted to the anterior portion of the olfactory cortex while those of the early-generated OB projection neurons innervate the entire olfactory cortex. Our results suggest that the late-generated mitral cells do not extend their axons to the posterior regions of the olfactory cortex. Therefore, the mitral cells having different birthdates differ, not only in cell body location and dendritic projections within the OB, but also in their axonal projection pattern to the olfactory cortex. 3 Significance Statement The olfactory bulb contains long-range projection neurons with distinct connectivity to higher order brain regions. Here, we examined how the birthdate of the olfactory bulb projection neurons correlates to the generation of differential connectivity patterns. We used in utero electroporation and high-resolution 3D imaging of the whole mouse brain, and determined the topographically distinct axonal projection patterns of early-and late-generated olfactory bulb projection neurons. Our results show that the timing of neurogenesis is a determining factor for the innervation of olfactory bulb projection neurons and indicate that mitral cells having different birthdates are the origins of distinct olfactory information pathways. Our study provides novel insights into the formation of neuronal circuits processing multiple aspects of olfactory information.

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Quantitative Cellular-Resolution Map of the Oxytocin Receptor in Postnatally Developing Mouse Brains

Cited by 17 publications

References 65 publications

Whole brain wiring diagram of oxytocin system in adult mice

Whole brain wiring diagram of oxytocin system in adult mice

The cellular architecture of microvessels, pericytes and neuronal cell types in organizing regional brain energy homeostasis in mice

Topographically Distinct Projection Patterns of Early-Generated and Late-Generated Projection Neurons in the Mouse Olfactory Bulb

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