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A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors.

Cell | Sep 22, 2016

The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female sociosexual behavior. Here, we show that, in male mice, OxtrINs regulate anxiety-related behaviors. We demonstrate that corticotropin-releasing-hormone-binding protein (CRHBP), an antagonist of the stress hormone CRH, is specifically expressed in OxtrINs. Production of CRHBP blocks the CRH-induced potentiation of postsynaptic layer 2/3 pyramidal cell activity of male, but not female, mice, thus producing an anxiolytic effect. Our data identify OxtrINs as critical for modulation of social and emotional behaviors in both females and males and reveal a molecular mechanism that acts on local medial prefrontal cortex (mPFC) circuits to coordinate responses to OXT and CRH. They suggest that additional studies of the impact of the OXT/OXTR and CRHBP/CRH pathways in males and females will be important in development of gender-specific therapies.

Pubmed ID: 27641503 RIS Download

Mesh terms: Animals | Anxiety | Behavior, Animal | Carrier Proteins | Corticotropin-Releasing Hormone | Female | Interneurons | Long-Term Potentiation | Male | Metabolic Networks and Pathways | Mice | Oxytocin | Prefrontal Cortex | Receptors, Oxytocin | Sex Characteristics | Sex Factors

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Allen Mouse Brain Atlas

A genome-wide, three-dimensional map of gene expression in the adult mouse brain. Similar in scale to the Human Genome Project, the Atlas reveals the expression patterns of approximately 20,000 genes throughout the entire adult mouse brain down to the cellular level. The Allen Institute's inaugural project, the Atlas was completed in 2006. The Allen Brain Atlas of the mouse brain is an interactive, genome-wide image database of gene expression with ISH and Nissl images. A combination of RNA in situ hybridization data, detailed Reference Atlases and informatics analysis tools are integrated to provide a searchable digital atlas of gene expression. Together, these resources present a comprehensive online platform for exploration of the brain at the cellular and molecular level.

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Allen Institute for Brain Science

Independent 501(c)(3) nonprofit medical research organization dedicated to accelerating the understanding of how the human brain works. Utilizing the mouse model system, a multidisciplinary group of neuroscientists, molecular biologists, informaticists, engineers, mathematicians, statisticians, and computational biologists have joined together to investigate expression of 20,000 genes in the adult mouse brain and to map gene expression to a cellular level beyond neuroanatomic boundaries. The data generated from this joint effort is contained in the publicly available Allen Brain Atlas application. Molecular approaches to understanding the functional organization of the brain promise new insights into the relationships between genes, brain, behavior and disease. To facilitate such insights, the Allen Institute produces large-scale projects and makes the resulting data and tools freely available online to scientists worldwide. These open resources, all available at www.brain-map.org, are intended to foster scientific discovery and collaboration. Atlases: Allen Developing Mouse Brain Atlas: A map of gene expression in the developing mouse brain. Building on the Allen Mouse Brain Atlas, this atlas reveals gene expression patterns from embryonic through postnatal stages to provide information about both spatial and temporal regulation of gene expression. Allen Spinal Cord Atlas: A genome-wide map of gene expression throughout the adult and juvenile mouse spinal cord. The Atlas was made possible through the generous support of a diverse consortium of funders, representing disease organizations, foundations, and corporate and private donors. Allen Mouse Brain Atlas (formerly Allen Brain Atlas): A genome-wide, three-dimensional map of gene expression in the adult mouse brain. Similar in scale to the Human Genome Project, the Atlas reveals the expression patterns of approximately 20,000 genes throughout the entire adult mouse brain down to the cellular level. The Allen Institutes inaugural project, the Atlas was completed in 2006. Studies: Mouse Diversity Study: Characterization of gene expression in the brain across genetic backgrounds and sex. Expanding on the Allen Mouse Brain Atlas, this resource includes data for 49 pharmaceutical drug target genes and a selected set of additional genes across seven mouse strains and in female mice. Transgenic Mouse Study: Comprehensive characterization of the expression patterns of genetically-controlled markers or tool genes in the brains of transgenic mice. Providing standardized, detailed, anatomical profiling of transgene expression throughout the brain, this dataset is intended to reveal the potential of each transgenic mouse line and help researchers choose the appropriate tools for their studies. Human Cortex Study: A collection of gene expression data in the adult human neocortex. Providing data for several categories of genes across different cortical regions and human individuals, including control and schizophrenic cases, the dataset has the potential to enable exploration of variability in cortical gene expression across different ages, between genders across different regions of the cortex and in schizophrenia. Sleep Study: A comprehensive collection of gene expression data in the mouse brain for five different conditions of sleep and wakefulness. Generated in collaboration with SRI International, this unique dataset is intended to help sleep researchers advance understanding of sleep deprivation and the dynamic changes underlying sleep/wake cycles. The sleep study was funded by an award from the U.S. Department of Defense.

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