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2. Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior

Author

Smith, Mark A., Choudhury, Agharul I., Glegola, Justyna A., Viskaitis, Paulius, Irvine, Elaine E., de Campos Silva, Pedro Caldas Custodio, Khadayate, Sanjay, Zeilhofer, Hanns Ulrich, and Withers, Dominic J.

Subjects
Endogenous opioids, GABA, Neurons, Obesity, Brain, Neuropeptides, Peptides, Health care industry, Stanford University
Abstract

Arcuate nucleus agouti-related peptide (AgRP) neurons play a central role in feeding and are under complex regulation by both homeostatic hormonal and nutrient signals and hypothalamic neuronal pathways. Feeding may also be influenced by environmental cues, sensory inputs, and other behaviors, implying the involvement of higher brain regions. However, whether such pathways modulate feeding through direct synaptic control of AgRP neuron activity is unknown. Here, we show that nociceptin-expressing neurons in the anterior bed nuclei of the stria terminalis (aBNST) make direct GABAergic inputs onto AgRP neurons. We found that activation of these neurons inhibited AgRP neurons and feeding. The activity of these neurons increased upon food availability, and their ablation resulted in obesity. Furthermore, these neurons received afferent inputs from a range of upstream brain regions as well as hypothalamic nuclei. Therefore, aBNST GABAergic nociceptin neurons may act as a gateway to feeding behavior by connecting AgRP neurons to both homeostatic and nonhomeostatic neuronal inputs., Introduction Feeding requires the integration of multiple neuronal networks to elicit appropriate behavioral and metabolic responses (1-3). These networks are sensitive to a range of modulatory inputs including nutrients and [...]

Published
2020
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4. Cardiac glycosides are broad-spectrum senolytics

Author

Guerrero, Ana, Herranz, Nicolás, Sun, Bin, Wagner, Verena, Gallage, Suchira, Guiho, Romain, Wolter, Katharina, Pombo, Joaquim, Irvine, Elaine E., Innes, Andrew J., Birch, Jodie, Glegola, Justyna, Manshaei, Saba, Heide, Danijela, Dharmalingam, Gopuraja, Harbig, Jule, Olona, Antoni, Behmoaras, Jacques, Dauch, Daniel, Uren, Anthony G., Zender, Lars, Vernia, Santiago, Martínez-Barbera, Juan Pedro, Heikenwalder, Mathias, Withers, Dominic J., and Gil, Jesús

Published
2019
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7. Reproducing the dopamine pathophysiology of schizophrenia and approaches to ameliorate it: a translational imaging study with ketamine

Author

Kokkinou, Michelle, primary, Irvine, Elaine E., additional, Bonsall, David R., additional, Natesan, Sridhar, additional, Wells, Lisa A., additional, Smith, Mark, additional, Glegola, Justyna, additional, Paul, Eleanor J., additional, Tossell, Kyoko, additional, Veronese, Mattia, additional, Khadayate, Sanjay, additional, Dedic, Nina, additional, Hopkins, Seth C., additional, Ungless, Mark A., additional, Withers, Dominic J., additional, and Howes, Oliver D., additional

Published
2020
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8. Gene replacement ameliorates deficits in mouse and human models of cyclin-dependent kinase-like 5 disorder

Author

Gao, Yunan, primary, Irvine, Elaine E, primary, Eleftheriadou, Ioanna, primary, Naranjo, Carlos Jiménez, primary, Hearn-Yeates, Francesca, primary, Bosch, Leontien, primary, Glegola, Justyna A, primary, Murdoch, Leah, primary, Czerniak, Aleksandra, primary, Meloni, Ilaria, primary, Renieri, Alessandra, primary, Kinali, Maria, primary, and Mazarakis, Nicholas D, primary

Published
2020
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9. Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior

Author

Smith, Mark A, Choudhury, Agharul I, Glegola, Justyna A, Viskaitis, Paulius, Irvine, Elaine E, De Campos Silva, Pedro Caldas Custodio, Khadayate, Sanjay, Zeilhofer, Hanns Ulrich; https://orcid.org/0000-0001-6954-4629, Withers, Dominic J, Smith, Mark A, Choudhury, Agharul I, Glegola, Justyna A, Viskaitis, Paulius, Irvine, Elaine E, De Campos Silva, Pedro Caldas Custodio, Khadayate, Sanjay, Zeilhofer, Hanns Ulrich; https://orcid.org/0000-0001-6954-4629, and Withers, Dominic J

Abstract

Arcuate nucleus agouti-related peptide (AgRP) neurons play a central role in feeding and are under complex regulation by both homeostatic hormonal and nutrient signals and hypothalamic neuronal pathways. Feeding may also be influenced by environmental cues, sensory inputs and other behaviors implying the involvement of higher brain regions. However, whether such pathways modulate feeding through direct synaptic control of AgRP neuron activity is unknown. Here we show that nociceptin-expressing neurons in the anterior bed nuclei of the stria terminalis (aBNST) make direct GABAergic inputs onto AgRP neurons. We found that activation of these neurons inhibited AgRP neurons and feeding. Activity of these neurons increased upon food availability and their ablation resulted in obesity. Furthermore, these neurons received afferent inputs from a range of upstream brain regions as well as hypothalamic nuclei. Therefore, aBNST nociceptin/GABAergic neurons may act as a gateway to feeding behavior by connecting AgRP neurons to both homeostatic and non-homeostatic neuronal inputs.

Published
2019

11. Mesocorticolimbic circuit mechanisms underlying the effects of ketamine on dopamine: a translational imaging study

Author

Kokkinou, Michelle, primary, Irvine, Elaine E., additional, Bonsall, David R., additional, Natesan, Sridhar, additional, Wells, Lisa A., additional, Smith, Mark, additional, Glegola, Justyna, additional, Paul, Eleanor J., additional, Tossell, Kyoko, additional, Veronese, Mattia, additional, Khadayate, Sanjay, additional, Dedic, Nina, additional, Hopkins, Seth C., additional, Ungless, Mark A., additional, Withers, Dominic J., additional, and Howes, Oliver D., additional

Published
2019
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