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7 Publications

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    Sternson Lab
    12/24/15 | An emerging technology framework for the neurobiology of appetite.
    Sternson SM, Atasoy D, Betley JN, Henry FE, Xu S
    Cell Metabolism. 2015 Dec 24;23(2):234-53. doi: 10.1016/j.cmet.2015.12.002

    Advances 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.

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    Sternson Lab
    11/04/15 | Applying the brakes: when to stop eating.
    Betley JN, Sternson SM
    Neuron. 2015 Nov 4;88(3):440-1. doi: 10.1016/j.neuron.2015.10.034

    The nucleus accumbens regulates consummatory behaviors, such as eating. In this issue of Neuron, O'Connor et al. (2015) identify dopamine receptor 1-expressing neurons that project to the lateral hypothalamus as mediating rapid control over feeding behavior.

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    Sternson Lab
    10/26/15 | Hunger: The carrot and the stick.
    Sternson SM
    Molecular Metabolism. 2016 Jan;5(1):1-2. doi: 10.1016/j.molmet.2015.10.002
    Sternson Lab
    09/11/15 | Cell type-specific pharmacology of NMDA receptors using masked MK801.
    Yang Y, Lee P, Sternson SM
    eLife. 2015 Sep 11;4:. doi: 10.7554/eLife.10206

    N-Methyl-D-aspartate receptors (NMDA-Rs) are ion channels that are important for synaptic plasticity, which is involved in learning and drug addiction. We show enzymatic targeting of an NMDA-R antagonist, MK801, to a molecularly defined neuronal population with the cell-type-selectivity of genetic methods and the temporal control of pharmacology. We find that NMDA-Rs on dopamine neurons are necessary for cocaine-induced synaptic potentiation, demonstrating that cell type-specific pharmacology can be used to dissect signaling pathways within complex brain circuits.

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    Sternson Lab
    09/02/15 | Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.
    Henry FE, Sugino K, Tozer A, Branco T, Sternson SM
    eLife. 2015 Sep 2;4:. doi: 10.7554/eLife.09800

    Molecular and cellular processes in neurons are critical for sensing and responding to energy deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss, and here we report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived young adult mice. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite and body weight. We find that AGRP neurons are considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion channels, neuropeptides, and receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders.

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    Sternson Lab
    08/26/15 | Optogenetics: 10 years after ChR2 in neurons-views from the community.
    Adamantidis A, Arber S, Bains JS, Bamberg E, Bonci A, Buzsáki G, Cardin JA, Costa RM, Dan Y, Goda Y, Graybiel AM, Häusser M, Hegemann P, Huguenard JR, Insel TR, Janak PH, Johnston D, Josselyn SA, Koch C, Kreitzer AC, Lüscher C, Malenka RC, Miesenböck G, Nagel G, Roska B, Schnitzer MJ, Shenoy KV, Soltesz I, Sternson SM, Tsien RW, Tsien RY, Turrigiano GG, Tye KM, Wilson RI
    Nature Neuroscience. 2015 Aug 26;18(9):1202-12. doi: 10.1038/nn.4106
    04/27/15 | Neurons for hunger and thirst transmit a negative-valence teaching signal.
    Betley JN, Xu S, Cao ZF, Gong R, Magnus CJ, Yu Y, Sternson SM
    Nature. 2015 Apr 27;521(7551):180-5. doi: 10.1038/nature14416

    Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.

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