Molecular Tools Core

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Project Summary: Molecular Tools Core One of the major features of this BRAIN Initiative proposal on “Oxytocin Modulation of Neural Circuit Function and Behavior” is this Molecular Tools Research Support Core. Each of the Project teams is examining oxytocin release and the action of oxytocin receptor signaling. Oxytocin is exemplary among peptide hormones and neuromodulators, has been studied in various forms for over a century, and has clear physiological action, behavioral relevance, and biomedical importance. However, little is known about the cellular and network effects of oxytocin signaling. This is in part due to lack of specific antibodies for determining which brain areas and cell types express oxytocin receptors, as well as other molecular tools for specifically manipulating and monitoring oxytocin signaling with high spatiotemporal precision. Our labs have generated, validated, and are distributing the first specific antibodies to mouse oxytocin receptors, and have also developed the first successful versions of caged oxytocin compounds. Given the successful use and enthusiasm by the scientific community together with the need for continued validation and optimization, we feel obliged to scale-up production of these reagents and improve their functionality. There is clearly urgent and widespread need for these resources, which are best produced, tested, and distributed by a Core facility rather than by individual labs. Aim 1 of the Molecular Tools Core is to continue production of oxytocin receptor antibodies, distribute these antibodies broadly, and optimize their utility and specificity including generation of monoclonal antibodies. Aim 2 is to generate and optimize caged and photo-switchable forms of oxytocin receptor agonists and antagonists, useful for delineating specifically when and where oxytocin receptor signaling acts to generate physiological responses in the central nervous system and in peripheral tissues. Aim 3 generates reagents for click chemistry involving tagged oxytocin, to visualize oxytocin within fixed and live tissue, to help determine if and where exogenous oxytocin delivery acts within an organism. Aim 4 is to generate useful and when needed develop new mouse lines for cell-type specific dissection of oxytocinergic signaling, and to leverage transcriptome data and other gene expression resources to facilitate studies on the roles of molecularly defined Oxt+ and Oxtr+ populations in socio-spatial behavior.