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Öğe A genetically specified connectomics approach applied to long-range feeding regulatory circuits(Nature Publishing Group, 2014) Atasoy, Deniz; Betley, Jan Nicholas; Li, Wei-Ping; Hong Su, Helen; Sertel, Sinem M.; Scheffer, Louis K.; Simpson, Julie H.; Fetter, Richard D.; Sternson, Scott M.Synaptic connectivity and molecular composition provide a blueprint for information processing in neural circuits. Detailed structural analysis of neural circuits requires nanometer resolution, which can be obtained with serial-section electron microscopy. However, this technique remains challenging for reconstructing molecularly defined synapses. We used a genetically encoded synaptic marker for electron microscopy (GESEM) based on intra-vesicular generation of electron-dense labeling in axonal boutons. This approach allowed the identification of synapses from Cre recombinase expressing or GAL4-expressing neurons in the mouse and fly with excellent preservation of ultrastructure. We applied this tool to visualize long-range connectivity of AGRP and POMC neurons in the mouse, two molecularly defined hypothalamic populations that are important for feeding behavior. Combining selective ultrastructural reconstruction of neuropil with functional and viral circuit mapping, we characterized some basic features of circuit organization for axon projections of these cell types. Our findings demonstrate that GESEM labeling enables long-range connectomics with molecularly defined cell types.Öğe Agouti-related protein neuron circuits that regulate appetite(Karger, 2014) Sternson, Scott M.; Atasoy, DenizNew tools for mapping and manipulating molecularly defined neural circuits have improved the understanding of how the central nervous system regulates appetite. Studies that focused on Agouti-related protein neurons, a starvation-sensitive hypothalamic population, have identified multiple circuit elements that can elicit or suppress feeding behavior. Distinct axon projections of this neuron population point to different circuits that regulate long-term appetite, short-term feeding, or visceral malaise-mediated anorexia. Here, we review recent studies examining these neural circuits that control food intake.Öğe An emerging technology framework for the neurobiology of appetite(Cell Press, 2016) Sternson, Scott M.; Atasoy, Deniz; Betley, J. Nicholas; Henry, Fredrick E.; Xu, ShengjinAdvances in neuro-technology for mapping, manipulating, and monitoring molecularly defined cell types are rapidly advancing insight into neural circuits that regulate appetite. Here, we review these important tools and their applications in circuits that control food seeking and consumption. Technical capabilities provided by these tools establish a rigorous experimental framework for research into the neurobiology of hunger.Öğe Chemogenetic tools for causal cellular and neuronal biology(American Physiological Society, 2018) Atasoy, Deniz; Sternson, Scott M.Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo.Öğe Functional and anatomical dissection of feeding circuits(Wiley, 2016) Atasoy, Deniz; Sternson, Scott M.This chapter reviews the application of new genetically encoded tools in feeding circuits that regulate appetite. Rapid activation and inhibition of agouti related peptide (AgRP) neurons conclusively established a causal role for rapid control of food intake. Chemogenetic activation of AgRP neurons using hM3Dq avoids the invasive protocols required for ChR2 activation. ChR2 distributes into axons, and selective optogenetic activation of AgRP neuron axon projection fields in distinct brain areas was used to examine their individual contribution to feeding behavior. Some of the brain areas targeted by AgRP neuron axon projections have been examined further for cell type specific control of appetite. Rodents with bed nucleus of stria terminalis (BNST) lesions show hyperphagia and obesity, indicating that reduced BNST output promotes feeding. pro-opiomelanocortin (POMC) neurons regulate feeding over longer timescales. parabrachial nucleus (PBN) neurons have a powerful inhibitory role on food intake, but their inhibition does not strongly elevate food intake.











