Ghrelin and Orexin Interact to Increase Meal Size Through a Descending Hippocampus to Hindbrain Signaling Pathway

  • Andrea N. Suarez
    Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California
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  • Clarissa M. Liu
    Neuroscience Graduate Program, University of Southern California, Los Angeles, California
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  • Alyssa M. Cortella
    Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California
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  • Emily E. Noble
    Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California

    Department of Foods and Nutrition, University of Georgia, Athens, Georgia
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  • Scott E. Kanoski
    Address correspondence to Scott E. Kanoski, Ph.D., Department of Biological Sciences, University of Southern California, 3560 Watt Way, PED 107, Los Angeles, CA 90089-0652.
    Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California

    Neuroscience Graduate Program, University of Southern California, Los Angeles, California
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      Memory and cognitive processes influence the amount of food consumed during a meal, yet the neurobiological mechanisms mediating these effects are poorly understood. The hippocampus (HPC) has recently emerged as a brain region that integrates feeding-relevant biological signals with learning and memory processes to regulate feeding. We investigated whether the gut-derived hormone ghrelin acts in the ventral HPC (vHPC) to increase meal size through interactions with gut-derived satiation signaling.


      Interactions between vHPC ghrelin signaling, gut-derived satiation signaling, feeding, and interoceptive discrimination learning were assessed via rodent behavioral neuropharmacological approaches. Downstream neural pathways were identified using transsynaptic virus-based tracing strategies.


      vHPC ghrelin signaling counteracted the food intake–reducing effects produced by various peripheral biological satiation signals, including cholecystokinin, exendin-4 (a glucagon-like peptide-1 receptor agonist), amylin, and mechanical distension of the stomach. Furthermore, vHPC ghrelin signaling produced interoceptive cues that generalized to a perceived state of energy deficit, thereby providing a potential mechanism for the attenuation of satiation processing. Neuroanatomical tracing identified a multiorder connection from vHPC neurons to lateral hypothalamic area orexin (hypocretin)-producing neurons that project to the laterodorsal tegmental nucleus in the hindbrain. Lastly, vHPC ghrelin signaling increased spontaneous meal size via downstream orexin receptor signaling in the laterodorsal tegmental nucleus.


      vHPC ghrelin signaling increases meal size by counteracting the efficacy of various gut-derived satiation signals. These effects occur via downstream orexin signaling to the hindbrain laterodorsal tegmental nucleus, thereby highlighting a novel hippocampus-hypothalamus-hindbrain pathway regulating meal size control.


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        • Woods S.C.
        • Seeley R.J.
        Adiposity signals and the control of energy homeostasis.
        Nutrition. 2000; 16: 894-902
        • Leibowitz S.F.
        • Wortley K.E.
        Hypothalamic control of energy balance: Different peptides, different functions.
        Peptides. 2004; 25: 473-504
        • Narayanan N.S.
        • Guarnieri D.J.
        • DiLeone R.J.
        Metabolic hormones, dopamine circuits, and feeding.
        Front Neuroendocrinol. 2010; 31: 104-112
        • Grill H.J.
        • Hayes M.R.
        Hindbrain neurons as an essential hub in the neuroanatomically distributed control of energy balance.
        Cell Metab. 2012; 16: 296-309
        • Liu C.M.
        • Kanoski S.E.
        Homeostatic and non-homeostatic controls of feeding behavior: Distinct vs. common neural systems.
        Physiol Behav. 2018; 193: 223-231
        • Hsu T.M.
        • McCutcheon J.E.
        • Roitman M.F.
        Parallels and overlap: The integration of homeostatic signals by mesolimbic dopamine neurons.
        Front Psychiatry. 2018; 9: 410
        • Azevedo E.P.
        • Pomeranz L.
        • Cheng J.
        • Schneeberger M.
        • Vaughan R.
        • Stern S.A.
        • et al.
        A role of Drd2 hippocampal neurons in context-dependent food intake.
        Neuron. 2019; 102: 873-886.e875
        • Eichenbaum H.
        The hippocampus and declarative memory: Cognitive mechanisms and neural codes.
        Behav Brain Res. 2001; 127: 199-207
        • Moser E.I.
        • Moser M.B.
        • McNaughton B.L.
        Spatial representation in the hippocampal formation: A history.
        Nat Neurosci. 2017; 20: 1448-1464
        • Kanoski S.E.
        • Grill H.J.
        Hippocampus contributions to food intake control: Mnemonic, neuroanatomical, and endocrine mechanisms.
        Biol Psychiatry. 2017; 81: 748-756
        • Parent M.B.
        • Darling J.N.
        • Henderson Y.O.
        Remembering to eat: Hippocampal regulation of meal onset.
        Am J Physiol Regul Integr Comp Physiol. 2014; 306: R701-R713
        • Davidson T.L.
        • Jones S.
        • Roy M.
        • Stevenson R.J.
        The cognitive control of eating and body weight: It’s more than what you “think”.
        Front Psychol. 2019; 10: 62
        • Min D.K.
        • Tuor U.I.
        • Koopmans H.S.
        • Chelikani P.K.
        Changes in differential functional magnetic resonance signals in the rodent brain elicited by mixed-nutrient or protein-enriched meals.
        Gastroenterology. 2011; 141: 1832-1841
        • Min D.K.
        • Tuor U.I.
        • Chelikani P.K.
        Gastric distention induced functional magnetic resonance signal changes in the rodent brain.
        Neuroscience. 2011; 179: 151-158
        • Wang G.J.
        • Yang J.
        • Volkow N.D.
        • Telang F.
        • Ma Y.
        • Zhu W.
        • et al.
        Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry.
        Proc Natl Acad Sci U S A. 2006; 103: 15641-15645
        • Suarez A.N.
        • Hsu T.M.
        • Liu C.M.
        • Noble E.E.
        • Cortella A.M.
        • Nakamoto E.M.
        • et al.
        Gut vagal sensory signaling regulates hippocampus function through multi-order pathways.
        Nat Commun. 2018; 9: 2181
        • Kanoski S.E.
        • Hayes M.R.
        • Greenwald H.S.
        • Fortin S.M.
        • Gianessi C.A.
        • Gilbert J.R.
        • et al.
        Hippocampal leptin signaling reduces food intake and modulates food-related memory processing.
        Neuropsychopharmacology. 2011; 36: 1859-1870
        • Hsu T.M.
        • Noble E.E.
        • Liu C.M.
        • Cortella A.M.
        • Konanur V.R.
        • Suarez A.N.
        • et al.
        A hippocampus to prefrontal cortex neural pathway inhibits food motivation through glucagon-like peptide-1 signaling.
        Mol Psychiatry. 2018; 23: 1555-1565
        • Hsu T.M.
        • Hahn J.D.
        • Konanur V.R.
        • Noble E.E.
        • Suarez A.N.
        • Thai J.
        • et al.
        Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways.
        Elife. 2015; 4
        • Sun Y.
        • Wang P.
        • Zheng H.
        • Smith R.G.
        Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor.
        Proc Natl Acad Sci U S A. 2004; 101: 4679-4684
        • Howard A.D.
        • Feighner S.D.
        • Cully D.F.
        • Arena J.P.
        • Liberator P.A.
        • Rosenblum C.I.
        • et al.
        A receptor in pituitary and hypothalamus that functions in growth hormone release.
        Science. 1996; 273: 974-977
        • Cummings D.E.
        • Purnell J.Q.
        • Frayo R.S.
        • Schmidova K.
        • Wisse B.E.
        • Weigle D.S.
        A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.
        Diabetes. 2001; 50: 1714-1719
        • Drazen D.L.
        • Vahl T.P.
        • D’Alessio D.A.
        • Seeley R.J.
        • Woods S.C.
        Effects of a fixed meal pattern on ghrelin secretion: Evidence for a learned response independent of nutrient status.
        Endocrinology. 2006; 147: 23-30
        • Blum I.D.
        • Patterson Z.
        • Khazall R.
        • Lamont E.W.
        • Sleeman M.W.
        • Horvath T.L.
        • et al.
        Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice.
        Neuroscience. 2009; 164: 351-359
        • Callahan H.S.
        • Cummings D.E.
        • Pepe M.S.
        • Breen P.A.
        • Matthys C.C.
        • Weigle D.S.
        Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans.
        J Clin Endocrinol Metab. 2004; 89: 1319-1324
        • Ariyasu H.
        • Takaya K.
        • Tagami T.
        • Ogawa Y.
        • Hosoda K.
        • Akamizu T.
        • et al.
        Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans.
        J Clin Endocrinol Metab. 2001; 86: 4753-4758
        • Cao S.G.
        • Wu H.
        • Cai Z.Z.
        Dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action.
        Kaohsiung J Med Sci. 2016; 32: 113-117
        • Levin F.
        • Edholm T.
        • Schmidt P.T.
        • Gryback P.
        • Jacobsson H.
        • Degerblad M.
        • et al.
        Ghrelin stimulates gastric emptying and hunger in normal-weight humans.
        J Clin Endocrinol Metab. 2006; 91: 3296-3302
        • Cabral A.
        • Cornejo M.P.
        • Fernandez G.
        • De Francesco P.N.
        • Garcia-Romero G.
        • Uriarte M.
        • et al.
        Circulating ghrelin acts on GABA neurons of the area postrema and mediates gastric emptying in male mice.
        Endocrinology. 2017; 158: 1436-1449
        • Williams D.L.
        • Grill H.J.
        • Cummings D.E.
        • Kaplan J.M.
        Vagotomy dissociates short- and long-term controls of circulating ghrelin.
        Endocrinology. 2003; 144: 5184-5187
        • Woods S.C.
        Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake.
        Am J Physiol Gastrointest Liver Physiol. 2004; 286: G7-G13
        • Moran T.H.
        Gut peptides in the control of food intake: 30 years of ideas.
        Physiol Behav. 2004; 82: 175-180
        • Diano S.
        • Farr S.A.
        • Benoit S.C.
        • McNay E.C.
        • da Silva I.
        • Horvath B.
        • et al.
        Ghrelin controls hippocampal spine synapse density and memory performance.
        Nat Neurosci. 2006; 9: 381-388
        • Guan X.M.
        • Yu H.
        • Palyha O.C.
        • McKee K.K.
        • Feighner S.D.
        • Sirinathsinghji D.J.
        • et al.
        Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues.
        Brain Res Mol Brain Res. 1997; 48: 23-29
        • Zigman J.M.
        • Jones J.E.
        • Lee C.E.
        • Saper C.B.
        • Elmquist J.K.
        Expression of ghrelin receptor mRNA in the rat and the mouse brain.
        J Comp Neurol. 2006; 494: 528-548
        • Mani B.K.
        • Walker A.K.
        • Lopez Soto E.J.
        • Raingo J.
        • Lee C.E.
        • Perello M.
        • et al.
        Neuroanatomical characterization of a growth hormone secretagogue receptor-green fluorescent protein reporter mouse.
        J Comp Neurol. 2014; 522: 3644-3666
        • Kanoski S.E.
        • Fortin S.M.
        • Ricks K.M.
        • Grill H.J.
        Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K-Akt signaling.
        Biol Psychiatry. 2013; 73: 915-923
        • Hsu T.M.
        • Noble E.E.
        • Reiner D.J.
        • Liu C.M.
        • Suarez A.N.
        • Konanur V.R.
        • et al.
        Hippocampus ghrelin receptor signaling promotes socially-mediated learned food preference.
        Neuropharmacology. 2018; 131: 487-496
        • Xu L.
        • Gong Y.
        • Wang H.
        • Sun X.
        • Guo F.
        • Gao S.
        • et al.
        The stimulating effect of ghrelin on gastric motility and firing activity of gastric-distension-sensitive hippocampal neurons and its underlying regulation by the hypothalamus.
        Exp Physiol. 2014; 99: 123-135
        • Cone J.J.
        • McCutcheon J.E.
        • Roitman M.F.
        Ghrelin acts as an interface between physiological state and phasic dopamine signaling.
        J Neurosci. 2014; 34: 4905-4913
        • Brown J.A.
        • Bugescu R.
        • Mayer T.A.
        • Gata-Garcia A.
        • Kurt G.
        • Woodworth H.L.
        • et al.
        Loss of action via neurotensin-leptin receptor neurons disrupts leptin and ghrelin-mediated control of energy balance.
        Endocrinology. 2017; 158: 1271-1288
        • Moran T.H.
        • Baldessarini A.R.
        • Salorio C.F.
        • Lowery T.
        • Schwartz G.J.
        Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin.
        Am J Physiol. 1997; 272: R1245-R1251
        • Scarpignato C.
        • Capovilla T.
        • Bertaccini G.
        Action of caerulein on gastric emptying of the conscious rat.
        Arch Int Pharmacodyn Ther. 1980; 246: 286-294
        • Bozkurt A.
        • Oktar B.K.
        • Kurtel H.
        • Alican I.
        • Coskun T.
        • Yegen B.C.
        Capsaicin-sensitive vagal fibres and 5-HT3-, gastrin releasing peptide- and cholecystokinin A-receptors are involved in distension-induced inhibition of gastric emptying in the rat.
        Regul Pept. 1999; 83: 81-86
        • Kanoski S.E.
        • Fortin S.M.
        • Arnold M.
        • Grill H.J.
        • Hayes M.R.
        Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4.
        Endocrinology. 2011; 152: 3103-3112
        • Lutz T.A.
        • Mollet A.
        • Rushing P.A.
        • Riediger T.
        • Scharrer E.
        The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats.
        Int J Obes Relat Metab Disord. 2001; 25: 1005-1011
        • Kanoski S.E.
        • Walls E.K.
        • Davidson T.L.
        Interoceptive “satiety” signals produced by leptin and CCK.
        Peptides. 2007; 28: 988-1002
        • Davidson T.L.
        • Kanoski S.E.
        • Tracy A.L.
        • Walls E.K.
        • Clegg D.
        • Benoit S.C.
        The interoceptive cue properties of ghrelin generalize to cues produced by food deprivation.
        Peptides. 2005; 26: 1602-1610
        • Davidson T.L.
        • Kanoski S.E.
        • Chan K.
        • Clegg D.J.
        • Benoit S.C.
        • Jarrard L.E.
        Hippocampal lesions impair retention of discriminative responding based on energy state cues.
        Behav Neurosci. 2010; 124: 97-105
        • Kennedy P.J.
        • Shapiro M.L.
        Retrieving memories via internal context requires the hippocampus.
        J Neurosci. 2004; 24: 6979-6985
        • Zingg B.
        • Chou X.L.
        • Zhang Z.G.
        • Mesik L.
        • Liang F.
        • Tao H.W.
        • et al.
        AAV-mediated anterograde transsynaptic tagging: Mapping corticocollicular input-defined neural pathways for defense behaviors.
        Neuron. 2017; 93: 33-47
        • Swanson L.W.
        Brain Maps: Structure of the Rat Brain.
        3rd ed. Academic Press, San Diego2004
        • Cenquizca L.A.
        • Swanson L.W.
        Analysis of direct hippocampal cortical field CA1 axonal projections to diencephalon in the rat.
        J Comp Neurol. 2006; 497: 101-114
        • Swanson L.W.
        • Cowan W.M.
        The connections of the septal region in the rat.
        J Comp Neurol. 1979; 186: 621-655
        • van Groen T.
        • Wyss J.M.
        Extrinsic projections from area CA1 of the rat hippocampus: Olfactory, cortical, subcortical, and bilateral hippocampal formation projections.
        J Comp Neurol. 1990; 302: 515-528
        • Cone J.J.
        • Roitman J.D.
        • Roitman M.F.
        Ghrelin regulates phasic dopamine and nucleus accumbens signaling evoked by food-predictive stimuli.
        J Neurochem. 2015; 133: 844-856
        • Reiner D.J.
        • Leon R.M.
        • McGrath L.E.
        • Koch-Laskowski K.
        • Hahn J.D.
        • Kanoski S.E.
        • et al.
        Glucagon-like peptide-1 receptor signaling in the lateral dorsal tegmental nucleus regulates energy balance.
        Neuropsychopharmacology. 2018; 43: 627-637
        • Seeley R.J.
        • Grill H.J.
        • Kaplan J.M.
        Neurological dissociation of gastrointestinal and metabolic contributions to meal size control.
        Behav Neurosci. 1994; 108: 347-352
        • Grill H.J.
        • Norgren R.
        Chronically decerebrate rats demonstrate satiation but not bait shyness.
        Science. 1978; 201: 267-269
        • Grill H.J.
        • Kaplan J.M.
        Sham feeding in intact and chronic decerebrate rats.
        Am J Physiol. 1992; 262: R1070-R1074
        • Ferriday D.
        • Brunstrom J.M.
        How does food-cue exposure lead to larger meal sizes?.
        Br J Nutr. 2008; 100: 1325-1332
        • Higgs S.
        Memory for recent eating and its influence on subsequent food intake.
        Appetite. 2002; 39: 159-166
        • Brunstrom J.M.
        • Burn J.F.
        • Sell N.R.
        • Collingwood J.M.
        • Rogers P.J.
        • Wilkinson L.L.
        • et al.
        Episodic memory and appetite regulationin humans.
        PLoS One. 2012; 7: e50707
        • Whitelock V.
        • Robinson E.
        Remembered meal satisfaction, satiety, and later snack food intake: A laboratory study.
        Nutrients. 2018; 10
        • Higgs S.
        • Thomas J.
        Social influences on eating.
        Curr Opin Behav Sciences. 2016; 9: 1-6
        • Hannapel R.
        • Ramesh J.
        • Ross A.
        • LaLumiere R.T.
        • Roseberry A.G.
        • Parent M.B.
        Postmeal optogenetic inhibition of dorsal or ventral hippocampal pyramidal neurons increases future intake.
        eNeuro. 2019; 6
        • Sweeney P.
        • Yang Y.
        An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding.
        Nat Commun. 2015; 6: 10188
        • Rozin P.
        • Dow S.
        • Moscovitch M.
        • Rajaram S.
        What causes humans to begin and end a meal? A role for memory for what has been eaten, as evidenced by a study of multiple meal eating in amnesic patients.
        Psychol Sci. 1998; 9: 392-396
        • Higgs S.
        • Williamson A.C.
        • Rotshtein P.
        • Humphreys G.W.
        Sensory-specific satiety is intact in amnesics who eat multiple meals.
        Psychol Sci. 2008; 19: 623-628
        • Sample C.H.
        • Martin A.A.
        • Jones S.
        • Hargrave S.L.
        • Davidson T.L.
        Western-style diet impairs stimulus control by food deprivation state cues: Implications for obesogenic environments.
        Appetite. 2015; 93: 13-23
        • Date Y.
        • Murakami N.
        • Toshinai K.
        • Matsukura S.
        • Niijima A.
        • Matsuo H.
        • et al.
        The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats.
        Gastroenterology. 2002; 123: 1120-1128
        • Arnold M.
        • Mura A.
        • Langhans W.
        • Geary N.
        Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat.
        J Neurosci. 2006; 26: 11052-11060
        • Del Prete E.
        • Balkowski G.
        • Scharrer E.
        Meal pattern of rats during hyperphagia induced by longterm food restriction is affected by diet composition.
        Appetite. 1994; 23: 79-86
        • Dess N.K.
        • Schreiber K.R.
        • Winter G.M.
        • Chapman C.D.
        Taste as a marker for behavioral energy regulation: Replication and extension of meal pattern evidence from selectively bred rats.
        Behav Processes. 2018; 153: 9-15
        • Hahn J.D.
        • Swanson L.W.
        Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat.
        Brain Res Rev. 2010; 64: 14-103
        • Estabrooke I.V.
        • McCarthy M.T.
        • Ko E.
        • Chou T.C.
        • Chemelli R.M.
        • Yanagisawa M.
        • et al.
        Fos expression in orexin neurons varies with behavioral state.
        J Neurosci. 2001; 21: 1656-1662
        • Harris G.C.
        • Aston-Jones G.
        Arousal and reward: a dichotomy in orexin function.
        Trends Neurosci. 2006; 29: 571-577
        • Aston-Jones G.
        • Smith R.J.
        • Sartor G.C.
        • Moorman D.E.
        • Massi L.
        • Tahsili-Fahadan P.
        • et al.
        Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction.
        Brain Res. 2010; 1314: 74-90
        • Aston-Jones G.
        • Smith R.J.
        • Moorman D.E.
        • Richardson K.A.
        Role of lateral hypothalamic orexin neurons in reward processing and addiction.
        Neuropharmacology. 2009; 56: 112-121
        • Boutrel B.
        • Kenny P.J.
        • Specio S.E.
        • Martin-Fardon R.
        • Markou A.
        • Koob G.F.
        • et al.
        Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior.
        Proc Natl Acad Sci U S A. 2005; 102: 19168-19173
        • Dickson S.L.
        • Egecioglu E.
        • Landgren S.
        • Skibicka K.P.
        • Engel J.A.
        • Jerlhag E.
        The role of the central ghrelin system in reward from food and chemical drugs.
        Mol Cell Endocrinol. 2011; 340: 80-87
        • Cornwall J.
        • Cooper J.D.
        • Phillipson O.T.
        Afferent and efferent connections of the laterodorsal tegmental nucleus in the rat.
        Brain Res Bull. 1990; 25: 271-284
        • Reiner D.J.
        • Mietlicki-Baase E.G.
        • Olivos D.R.
        • McGrath L.E.
        • Zimmer D.J.
        • Koch-Laskowski K.
        • et al.
        Amylin acts in the lateral dorsal tegmental nucleus to regulate energy balance through gamma-aminobutyric acid signaling.
        Biol Psychiatry. 2017; 82: 828-838
        • Cabral A.
        • Fernandez G.
        • Perello M.
        Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.
        Neuroscience. 2013; 253: 406-415
        • Lammel S.
        • Lim B.K.
        • Ran C.
        • Huang K.W.
        • Betley M.J.
        • Tye K.M.
        • et al.
        Input-specific control of reward and aversion in the ventral tegmental area.
        Nature. 2012; 491: 212-217
        • Schmidt H.D.
        • Famous K.R.
        • Pierce R.C.
        The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT.
        Eur J Neurosci. 2009; 30: 1358-1369
        • Jerlhag E.
        • Egecioglu E.
        • Dickson S.L.
        • Douhan A.
        • Svensson L.
        • Engel J.A.
        Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens.
        Addict Biol. 2007; 12: 6-16
        • Jerlhag E.
        • Janson A.C.
        • Waters S.
        • Engel J.A.
        Concomitant release of ventral tegmental acetylcholine and accumbal dopamine by ghrelin in rats.
        PLoS One. 2012; 7e49557
        • Jerlhag E.
        • Egecioglu E.
        • Landgren S.
        • Salome N.
        • Heilig M.
        • Moechars D.
        • et al.
        Requirement of central ghrelin signaling for alcohol reward.
        Proc Natl Acad Sci U S A. 2009; 106: 11318-11323
        • Semba K.
        • Fibiger H.C.
        Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: A retro- and antero-grade transport and immunohistochemical study.
        J Comp Neurol. 1992; 323: 387-410
        • Hong E.Y.
        • Yoon Y.S.
        • Lee H.S.
        Differential distribution of melanin-concentrating hormone (MCH)- and hypocretin (Hcrt)-immunoreactive neurons projecting to the mesopontine cholinergic complex in the rat.
        Brain Res. 2011; 1424: 20-31
        • Peyron C.
        • Tighe D.K.
        • van den Pol A.N.
        • de Lecea L.
        • Heller H.C.
        • Sutcliffe J.G.
        • et al.
        Neurons containing hypocretin (orexin) project to multiple neuronal systems.
        J Neurosci. 1998; 18: 9996-10015
        • Marcus J.N.
        • Aschkenasi C.J.
        • Lee C.E.
        • Chemelli R.M.
        • Saper C.B.
        • Yanagisawa M.
        • et al.
        Differential expression of orexin receptors 1 and 2 in the rat brain.
        J Comp Neurol. 2001; 435: 6-25
        • Hayes M.R.
        • Bradley L.
        • Grill H.J.
        Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling.
        Endocrinology. 2009; 150: 2654-2659
        • Hsu T.M.
        • Suarez A.N.
        • Kanoski S.E.
        Ghrelin: A link between memory and ingestive behavior.
        Physiol Behav. 2016; 162: 10-17

      Linked Article

      • Supersizing the Hippocampus: Ghrelin Effects on Meal Size
        Biological PsychiatryVol. 87Issue 11
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          Most students in the biological and psychological sciences will be able to recall the unforgettable Henry Molaison (H.M.)—an amnesic patient whose characterization revolutionized our understanding of memory. Less well-known, however, is the impact of H.M.’s medial temporal lobectomy on food intake, where his ability to interpret interoceptive hunger signals was greatly diminished. In fact, after fully consuming one meal, when a second was presented to him a mere 60 seconds later, H.M. set about consuming it at an identical rate as the first (1).
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