Encoding of an engram for food location by satiety-promoting Drd2 hippocampal neurons

2018 ◽  
Author(s):  
Estefania P. Azevedo ◽  
Lisa Pomeranz ◽  
Jia Cheng ◽  
Marc Schneeberger ◽  
Sarah Stern ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Entorhinal Cortex ◽  
Hippocampal Neurons ◽  
High Order ◽  
Lateral Septum ◽  
Reduce Food Intake ◽  
Top Down ◽  
Food Location ◽  
Dopamine 2 Receptor

SUMMARYAssociative learning guides feeding behavior in mammals in part by using cues that link location in space to food availability. However, the elements of the top-down circuitry encoding the memory of the location of food is largely unknown, as are the high-order processes that control satiety. Here we report that hippocampal dopamine 2 receptor (D2R) neurons are specifically activated by food and that modulation of their activity reduce food intake in mice. We also found that activation of these neurons interferes with the valence of food and the acquisition of a spatial memory linking food to a location via projections from the hippocampus to the lateral septum. Finally, we showed that inputs from lateral entorhinal cortex (LEC) to the hippocampus can also drive satiety via activation of D2R cells. These data describe a previously unidentified function for hippocampal D2R cells to regulate feeding behavior and identifies a LEC->Hippocampus->Septal high-order circuit that encodes the memory of food location.

scholarly journals Hippocampus ghrelin signaling mediates appetite through lateral hypothalamic orexin pathways

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ted M Hsu ◽  
Joel D Hahn ◽  
Vaibhav R Konanur ◽  
Emily E Noble ◽  
Andrea N Suarez ◽  
...  
Keyword(s):  
Food Intake ◽  
Environmental Factors ◽  
Feeding Behavior ◽  
Lateral Hypothalamus ◽  
Hippocampal Neurons ◽  
Neural System ◽  
Direct Response ◽  
Feeding Patterns ◽  
Neurobiological Substrates ◽  
Intake Control

Feeding behavior rarely occurs in direct response to metabolic deficit, yet the overwhelming majority of research on the biology of food intake control has focused on basic metabolic and homeostatic neurobiological substrates. Most animals, including humans, have habitual feeding patterns in which meals are consumed based on learned and/or environmental factors. Here we illuminate a novel neural system regulating higher-order aspects of feeding through which the gut-derived hormone ghrelin communicates with ventral hippocampus (vHP) neurons to stimulate meal-entrained conditioned appetite. Additional results show that the lateral hypothalamus (LHA) is a critical downstream substrate for vHP ghrelin-mediated hyperphagia and that vHP ghrelin activated neurons communicate directly with neurons in the LHA that express the neuropeptide, orexin. Furthermore, activation of downstream orexin-1 receptors is required for vHP ghrelin-mediated hyperphagia. These findings reveal novel neurobiological circuitry regulating appetite through which ghrelin signaling in hippocampal neurons engages LHA orexin signaling.

Hepatic portal glucose infusions decrease food intake and increase food preference

1986 ◽  
Vol 251 (1) ◽  
pp. R192-R196 ◽  
Author(s):  
M. G. Tordoff ◽  
M. I. Friedman
Keyword(s):  
Food Intake ◽  
Unconditioned Stimulus ◽  
Feeding Behavior ◽  
Food Preference ◽  
Glucose Infusion ◽  
Previous Experience ◽  
Reduce Food Intake ◽  
Test Situation ◽  
Decrease Food Intake ◽  
Hepatic Portal

We examined the contribution of experimental factors to the hepatic control of food intake. Rats with either hepatic portal or jugular catheters were infused four times with glucose (4.5 mg/min) and equitonic saline (2 ml/2 h). During the infusions their food contained nonnutritive chocolate or chicken flavor, depending on the infusate received. Hepatic portal glucose decreased food intake relative to saline and no infusion conditions, but jugular glucose did not. When allowed to choose between the flavors associated with each infusate, rats with hepatic portal catheters preferred the flavor eaten during glucose infusion, and rats with jugular catheters showed no preference. These results suggest that a mechanism located in the liver can reduce food intake without producing malaise and that portal glucose can act as an unconditioned stimulus for the acquisition of a learned food preference. Several reports that hepatic portal infusions do not alter feeding behavior may be explained by a failure to control for previous experience in the test situation.

Effects of neurosecretory protein GL on food intake and fat accumulation under different dietary nutrient compositions in rats

2021 ◽  
Author(s):  
Keisuke Fukumura ◽  
Kenshiro Shikano ◽  
Yuaki Narimatsu ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Body Mass ◽  
Mass Gain ◽  
Chow Diet ◽  
Tissue Mass ◽  
Fat Accumulation ◽  
Intracerebroventricular Infusion ◽  
Body Mass Gain ◽  
Sucrose Diet

Abstract We recently identified a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), which is involved in energy homeostasis in birds and mammals. However, whether the action of NPGL is influenced by nutritional composition remains unknown. Thus, we investigated the effect of chronic intracerebroventricular infusion of NPGL for 13 days on feeding behavior and body mass gain under a normal chow diet (NC), high-fat diet, high-sucrose diet (HSD), and medium-fat/medium-sucrose diet (MFSD) in rats. NPGL stimulated food intake of NC and MFSD, especially during the light period. By contrast, NPGL decreased body mass gain under NC and increased total white adipose tissue mass in HSD- and MFSD-fed rats. These data suggest that the effects of NPGL on feeding behavior, body mass gain, and fat accumulation depend on nutrient type. Among them, sucrose in diets seems to contribute to fat accumulation elicited by NPGL.

scholarly journals Impaired branched chain amino acid metabolism alters feeding behavior and increases orexigenic neuropeptide expression in the hypothalamus

2011 ◽  
Vol 212 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Megan N Purpera ◽  
Li Shen ◽  
Marzieh Taghavi ◽  
Heike Münzberg ◽  
Roy J Martin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Food Intake ◽  
Feeding Behavior ◽  
Control Diet ◽  
Peripheral Tissues ◽  
Protein Status ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
Branched Chain Aminotransferase ◽  
Deficient Mice

Elevation of dietary or brain leucine appears to suppress food intake via a mechanism involving mechanistic target of rapamycin, AMPK, and/or branched chain amino acid (BCAA) metabolism. Mice bearing a deletion of mitochondrial branched chain aminotransferase (BCATm), which is expressed in peripheral tissues (muscle) and brain glia, exhibit marked increases in circulating BCAAs. Here, we test whether this increase alters feeding behavior and brain neuropeptide expression. Circulating and brain levels of BCAAs were increased two- to four-fold in BCATm-deficient mice (KO). KO mice weighed less than controls (25.9 vs 20.4 g,P<0.01), but absolute food intake was relatively unchanged. In contrast to wild-type mice, KO mice preferred a low-BCAA diet to a control diet (P<0.05) but exhibited no change in preference for low- vs high-protein (HP) diets. KO mice also exhibited low leptin levels and increased hypothalamicNpyandAgrpmRNA. Normalization of circulating leptin levels had no effect on either food preference or the increasedNpyandAgrpmRNA expression. If BCAAs act as signals of protein status, one would expect reduced food intake, avoidance of dietary protein, and reduction in neuropeptide expression in BCATm-KO mice. Instead, these mice exhibit an increased expression of orexigenic neuropeptides and an avoidance of BCAAs but not HP. These data thus suggest that either BCAAs do not act as physiological signals of protein status or the loss of BCAA metabolism within brain glia impairs the detection of protein balance.

Long lasting changes in the spontaneous activity of hippocampal neurons following stimulation of the entorhinal cortex

1976 ◽  
Vol 1 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Sam A. Deadwyler ◽  
Valentin Gribkoff ◽  
Carl Cotman ◽  
Gary Lynch
Keyword(s):  
Spontaneous Activity ◽  
Entorhinal Cortex ◽  
Hippocampal Neurons ◽  
Stimulation Of

scholarly journals GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility

2012 ◽  
Vol 303 (7) ◽  
pp. E853-E864 ◽  
Author(s):  
Xinfu Guan ◽  
Xuemei Shi ◽  
Xiaojie Li ◽  
Benny Chang ◽  
Yi Wang ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Feeding Behavior ◽  
Gastric Motility ◽  
Late Onset ◽  
Physiological Role ◽  
Immune Defense ◽  
Melanocortin Receptor ◽  
Melanocortin System ◽  
Dorsomedial Nucleus

Glucagon-like peptides (GLP-1/2) are cosecreted from endocrine L cells in the gut and preproglucagonergic neurons in the brain. Peripheral GLP-2 action is essential for maintaining intestinal homeostasis, improving absorption efficiency and blood flow, promoting immune defense, and producing efficacy in treatment of gastrointestinal diseases. However, it is unknown if CNS GLP-2 plays a physiological role in the control of energy homeostasis. Since GLP-1/2 are cotranslated from preproglucagongene and coproduced by prohormone convertase-1, it is challenging to knockout GLP-2 only. Instead, our laboratory has generated a Glp2r-floxed mouse line to dissect cell-specific GLP-2 receptor GLP-2R) action in the regulation of energy balance. Our objective was to determine if GLP-2R in the hypothalamus modulates feeding behavior and gastric emptying. We show that Glp2r mRNA and protein are highly expressed in the arcuate nucleus and dorsomedial nucleus of the mouse hypothalamus. Using the Cre-LoxP system, we generated mice that lack Glp2r expression in POMC neurons (KO; mainly in the hypothalamus). The KO mice showed hyperphagic behavior (such as increases in food intake and meal frequency), accelerated gastric emptying (assessed by [13C]octanoic acid breath test), and late-onset obesity, yet there was no decrease in basal metabolic rate. Infusion of GLP-2 (2.5 nmol into the 4th ventricle) suppressed food intake and gastric emptying, while GLP-2-mediated effects were abolished in the melanocortin receptor-4 (MC4R) KO mice. We conclude that Glp2r deletion in POMC neurons enhances feeding behavior and gastric motility, whereas icv GLP-2R activation suppresses food intake and gastric emptying through the MC4R signaling pathway. This study indicates that CNS GLP-2R plays a physiological role in the control of feeding behavior and gastric emptying and that this is mediated probably through the melanocortin system.

scholarly journals CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Molecular Forms ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Sprague Dawley ◽  
Solid Meal ◽  
Sprague Dawley Rats ◽  
And Behavior

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.

Brain regulation of feeding behavior and food intake in fish

2000 ◽  
Vol 126 (4) ◽  
pp. 415-434 ◽  
Author(s):  
Xinwei Lin ◽  
Hélène Volkoff ◽  
Yuwaraj Narnaware ◽  
Nicholas J Bernier ◽  
Pierre Peyon ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior

Cholecystokinin is a Satiety Hormone in Humans at Physiological Post-Prandial Plasma Concentrations

1995 ◽  
Vol 89 (4) ◽  
pp. 375-381 ◽  
Author(s):  
Anne Ballinger ◽  
Lorraine McLoughlin ◽  
Sami Medbak ◽  
Michael Clark
Keyword(s):  
Food Intake ◽  
Test Meal ◽  
Plasma Concentrations ◽  
Standard Test ◽  
Saline Infusion ◽  
Reduce Food Intake ◽  
Subsequent Test ◽  
Gut Hormone ◽  
Plasma Cholecystokinin ◽  
Satiety Hormone

1. Intravenous infusions of the brain/gut hormone, cholecystokinin, have been shown to reduce food intake in a subsequent test meal. However, in previous studies the doses administered were large and likely to have produced plasma concentrations far in excess of the normal post-prandial range. 2. In this study cholecystokinin-8 was infused intravenously to six healthy subjects in doses that reproduced physiological post-prandial concentrations. Plasma concentrations of cholecystokinin were measured using a novel sensitive and specific radioimmunoassay. The effect of cholecystokinin-8 infusion on subsequent food intake in a standard test meal was compared with the effect of saline infusion in the same subjects. 3. Food intake (mean ± SEM) was significantly less during cholecystokinin (5092 ± 665 kJ) than during saline infusion (6418 ± 723 kJ, P = 0.03). During cholecystokinin infusion, plasma concentrations increased from 0.45 ± 0.06 pmol/l to 7.28 ± 2.43 pmol/l immediately before the meal. With saline infusion there was no premeal increase in plasma cholecystokinin concentration. 4. This paper describes a novel radioimmunoassay for measurement of plasma concentrations of cholecystokinin. Using this assay we have demonstrated that cholecystokinin is important in control of satiety in humans.

Chronic infusion of islet amyloid polypeptide causes anorexia in rats

1996 ◽  
Vol 271 (6) ◽  
pp. R1654-R1659 ◽  
Author(s):  
U. Arnelo ◽  
J. Permert ◽  
T. E. Adrian ◽  
J. Larsson ◽  
P. Westermark ◽  
...  
Keyword(s):  
Food Intake ◽  
Body Weight Gain ◽  
Islet Amyloid Polypeptide ◽  
Reduce Food Intake ◽  
Islet Amyloid ◽  
Minimal Effective Dose ◽  
Subcutaneous Infusion ◽  
Pathophysiological Role ◽  
Chronic Infusion ◽  
High Doses

Islet amyloid polypeptide (IAPP) is a hormonal peptide that at high doses has been shown to reduce food intake. In the present study, the dose-response effects of subcutaneous infusion of IAPP (0, 2, 7, and 25 pmol.kg-1.min-1) for 8 days on food intake and meal patterns in rats were investigated. At the end of the experiment, plasma was obtained and levels of IAPP were measured by radioimmunoassay. IAPP dose-dependently and transiently inhibited food intake. The minimal effective dose (2 pmol.kg-1.min-1) caused a small but significant (up to 14%, P < 0.01) inhibition of food intake that lasted 5 days. The highest dose administered (25 pmol.kg-1.min-1) had the greatest effect (up to 44%, P < 0.001), which lasted throughout the 8-day period. Reductions in feeding during light and dark phases occurred through a decrease in number of meals consumed rather than meal size or meal duration. IAPP also decreased body weight gain and water intake dose dependently. IAPP infusion of 2, 7, and 25 pmol.kg-1.min-1 increased plasma IAPP concentrations from a basal level of 10.3 +/- 0.7 pM to 35.1 +/- 5.4, 78.1 +/- 11.2, and 236.6 +/- 23.6 pM, respectively, values that are likely to be close to physiological and within the pathophysiological ranges. Thus IAPP may play an important physiological or pathophysiological role in control of food intake.

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