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McDougle M, de Araujo A, Singh A, Yang M, Braga I, Paille V, Mendez-Hernandez R, Vergara M, Woodie LN, Gour A, Sharma A, Urs N, Warren B, de Lartigue G. Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 2024; 36:393-407.e7. [PMID: 38242133 PMCID: PMC11898112 DOI: 10.1016/j.cmet.2023.12.014] [Citation(s) in RCA: 33] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 09/25/2023] [Accepted: 12/11/2023] [Indexed: 01/21/2024]
Abstract
Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.
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Affiliation(s)
- Molly McDougle
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Alan de Araujo
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA
| | - Arashdeep Singh
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Mingxin Yang
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Isadora Braga
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Vincent Paille
- Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA; UMR1280 Physiopathologie des adaptations nutritionnelles, INRAE, Institut des maladies de l'appareil digestif, Université de Nantes, Nantes, France
| | - Rebeca Mendez-Hernandez
- Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
| | - Macarena Vergara
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA
| | - Lauren N Woodie
- Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA
| | - Abhishek Gour
- Department of Pharmaceutics, University of Florida, Gainesville, FL, USA
| | - Abhisheak Sharma
- Department of Pharmaceutics, University of Florida, Gainesville, FL, USA
| | - Nikhil Urs
- Department of Pharmacology, University of Florida, Gainesville, FL, USA
| | - Brandon Warren
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA
| | - Guillaume de Lartigue
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
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Brierley DI, de Lartigue G. Reappraising the role of the vagus nerve in GLP-1-mediated regulation of eating. Br J Pharmacol 2021; 179:584-599. [PMID: 34185884 PMCID: PMC8714868 DOI: 10.1111/bph.15603] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/03/2021] [Accepted: 06/16/2021] [Indexed: 12/19/2022] Open
Abstract
Here, we provide a focused review of the evidence for the roles of the vagus nerve in mediating the regulatory effects of peripherally and centrally produced GLP-1 on eating behaviour and energy balance. We particularly focus on recent studies which have used selective genetic, viral, and transcriptomic approaches to provide important insights into the anatomical and functional organisation of GLP-1-mediated gut-brain signalling pathways. A number of these studies have challenged canonical ideas of how GLP-1 acts in the periphery and the brain to regulate eating behaviour, with important implications for the development of pharmacological treatments for obesity.
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Affiliation(s)
- Daniel I Brierley
- Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
| | - Guillaume de Lartigue
- Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, Florida, USA
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McDougle M, Quinn D, Diepenbroek C, Singh A, de la Serre C, de Lartigue G. Intact vagal gut-brain signalling prevents hyperphagia and excessive weight gain in response to high-fat high-sugar diet. Acta Physiol (Oxf) 2021; 231:e13530. [PMID: 32603548 PMCID: PMC7772266 DOI: 10.1111/apha.13530] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 06/23/2020] [Accepted: 06/23/2020] [Indexed: 01/02/2023]
Abstract
Aim The tools that have been used to assess the function of the vagus nerve lack specificity. This could explain discrepancies about the role of vagal gut‐brain signalling in long‐term control of energy balance. Here we use a validated approach to selectively ablate sensory vagal neurones that innervate the gut to determine the role of vagal gut‐brain signalling in the control of food intake, energy expenditure and glucose homoeostasis in response to different diets. Methods Rat nodose ganglia were injected bilaterally with either the neurotoxin saporin conjugated to the gastrointestinal hormone cholecystokinin (CCK), or unconjugated saporin as a control. Food intake, body weight, glucose tolerance and energy expenditure were measured in both groups in response to chow or high‐fat high‐sugar (HFHS) diet. Willingness to work for fat or sugar was assessed by progressive ratio for orally administered solutions, while post‐ingestive feedback was tested by measuring food intake after an isocaloric lipid or sucrose pre‐load. Results Vagal deafferentation of the gut increases meal number in lean chow‐fed rats. Switching to a HFHS diet exacerbates overeating and body weight gain. The breakpoint for sugar or fat solution did not differ between groups, suggesting that increased palatability may not drive HFHS‐induced hyperphagia. Instead, decreased satiation in response to intra‐gastric infusion of fat, but not sugar, promotes hyperphagia in CCK‐Saporin‐treated rats fed with HFHS diet. Conclusions We conclude that intact sensory vagal neurones prevent hyperphagia and exacerbation of weight gain in response to a HFHS diet by promoting lipid‐mediated satiation.
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Affiliation(s)
- Molly McDougle
- Department of Pharmacodynamics University of Florida Gainesville FL USA
- Center for Integrative Cardiovascular and Metabolic Disease University of Florida Gainesville FL USA
- The John B. Pierce Laboratory New Haven CT USA
| | | | - Charlene Diepenbroek
- The John B. Pierce Laboratory New Haven CT USA
- Department of Cellular and Molecular Physiology Yale Medical School New Haven CT USA
| | - Arashdeep Singh
- Department of Pharmacodynamics University of Florida Gainesville FL USA
- Center for Integrative Cardiovascular and Metabolic Disease University of Florida Gainesville FL USA
| | | | - Guillaume de Lartigue
- Department of Pharmacodynamics University of Florida Gainesville FL USA
- Center for Integrative Cardiovascular and Metabolic Disease University of Florida Gainesville FL USA
- The John B. Pierce Laboratory New Haven CT USA
- Department of Cellular and Molecular Physiology Yale Medical School New Haven CT USA
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Effects of methyl methacrylate on the excitability of the area postrema neurons in rats. J Oral Biosci 2020; 62:306-309. [PMID: 32931900 DOI: 10.1016/j.job.2020.09.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 08/31/2020] [Accepted: 08/14/2020] [Indexed: 11/21/2022]
Abstract
OBJECTIVES The aim of the present study is to demonstrate the effects of inhaled methyl methacrylate (MMA) on the excitability of neurons in the area postrema (AP). We also investigated the relation between vagal afferent inputs and responding cells in the AP. METHODS We set up two groups of experimental animals, such as rats inhaling MMA and rats inhaling room air. To visualize the changes of AP neuron excitability after inhalation of MMA for 90 min, c-Fos protein expression was identified and quantified by immunohistochemical analysis. Some rats receiving ventral gastric branch vagotomy were also subjected to the abovementioned experiment. RESULTS The number of c-Fos-immunoreactive (Fos-ir) cells in the MMA group was more than six times greater than that of the control group (statistically significant, p < 0.01). In vagotomized rats inhaling MMA, markedly smaller number of Fos-ir cells was identified in the AP compared to that of rats inhaling MMA without vagotomy. CONCLUSIONS These results indicate that inhalation of MMA increases neuronal excitability in the AP, suggesting that vagal afferent inputs are involved in the induction mechanism of Fos-ir cells by MMA.
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Place preferences induced by electrical stimulation of the external lateral parabrachial subnucleus in a sequential learning task: Place preferences induced by NLPBe stimulation. Behav Brain Res 2020; 381:112442. [PMID: 31862469 DOI: 10.1016/j.bbr.2019.112442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 12/16/2019] [Accepted: 12/16/2019] [Indexed: 11/22/2022]
Abstract
It is known that electrical stimulation of the external lateral parabrachial nucleus (NLPBe) can sustain concurrent taste and place learning. Place preferences can be learned through different procedures. Previous studies demonstrated that electrical stimulation of the PBNLe can generate aversive and preference place learning using concurrent procedures. In the concurrent procedure, the animals can move freely in the maze, and intracranial electrical stimulation is associated with their voluntary stay in one of the two maze compartments. However, the rewarding properties of most stimuli, whether natural or drugs of abuse, have usually been investigated using the sequential procedure, in which animals are confined while receiving the unconditioned stimulus and then undergo a choice test without stimulation in a later phase. This study examined whether this stimulation can sustain place preference learning in sequential tasks. Results demonstrated that place preferences can also be induced by the electrical stimulation of the NLBe using sequential procedures. These findings suggest that the NLPBe may form part of a brain reward axis that shares certain characteristics with those observed in the processing of natural rewarding agents and especially of drugs of abuse.
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Simon MJ, Zafra MA, Puerto A. Differential rewarding effects of electrical stimulation of the lateral hypothalamus and parabrachial complex: Functional characterization and the relevance of opioid systems and dopamine. J Psychopharmacol 2019; 33:1475-1490. [PMID: 31282233 DOI: 10.1177/0269881119855982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Since the discovery of rewarding intracranial self-stimulation by Olds and Milner, extensive data have been published on the biological basis of reward. Although participation of the mesolimbic dopaminergic system is well documented, its precise role has not been fully elucidated, and some authors have proposed the involvement of other neural systems in processing specific aspects of reinforced behaviour. AIMS AND METHODS We reviewed published data, including our own findings, on the rewarding effects induced by electrical stimulation of the lateral hypothalamus (LH) and of the external lateral parabrachial area (LPBe) - a brainstem region involved in processing the rewarding properties of natural and artificial substances - and compared its functional characteristics as observed in operant and non-operant behavioural procedures. RESULTS Brain circuits involved in the induction of preferences for stimuli associated with electrical stimulation of the LBPe appear to functionally and neurochemically differ from those activated by electrical stimulation of the LH. INTERPRETATION We discuss the possible involvement of the LPBe in processing emotional-affective aspects of the brain reward system.
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Affiliation(s)
- Maria J Simon
- Department of Psychobiology, Mind, Brain and Behaviour Research Center (CIMCYC), University of Granada, Granada, Spain
| | - Maria A Zafra
- Department of Psychobiology, Mind, Brain and Behaviour Research Center (CIMCYC), University of Granada, Granada, Spain
| | - Amadeo Puerto
- Department of Psychobiology, Mind, Brain and Behaviour Research Center (CIMCYC), University of Granada, Granada, Spain
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Tolerance to rewarding brain electrical stimulation: Differential effects of contingent and non-contingent activation of parabrachial complex and lateral hypothalamus. Behav Brain Res 2018; 336:15-21. [DOI: 10.1016/j.bbr.2017.08.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 08/14/2017] [Accepted: 08/17/2017] [Indexed: 01/03/2023]
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Zafra MA, Agüera AD, Molina F, Puerto A. Relevance of the nucleus of the solitary tract, gelatinous part, in learned preferences induced by intragastric nutrient administration. Appetite 2017; 118:90-96. [PMID: 28789870 DOI: 10.1016/j.appet.2017.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Revised: 08/02/2017] [Accepted: 08/03/2017] [Indexed: 12/18/2022]
Abstract
Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task. Results show that unlike neurologically intact animals, which learn this task correctly, animals lesioned in the gelatinous part of NST manifest a disruption of discrimination learning. Thus, intakes of the flavored stimulus paired with predigested liquid diet and of the flavored stimulus paired with physiological saline were virtually identical. However, SolG- and sham-lesioned groups consumed similar total amounts of both flavors. These findings suggest that SolG, as a relay of the vagus nerve, along with its anatomical projection, the external lateral parabrachial subnucleus (LPBe), may constitute an anatomical axis that is important in the induction of concurrent flavor/side preferences. It also appears to be relevant in other behavioral processes that require rapid processing of information from the upper gastrointestinal tract.
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Affiliation(s)
- María A Zafra
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain; Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Campus de Cartuja, Granada 18071, Spain.
| | - Antonio D Agüera
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain
| | - Filomena Molina
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain; Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Campus de Cartuja, Granada 18071, Spain
| | - Amadeo Puerto
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain; Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Campus de Cartuja, Granada 18071, Spain
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Zafra MA, Agüera AD, Molina F, Puerto A. Disruption of re-intake after partial withdrawal of gastric food contents in rats lesioned in the gelatinous part of the nucleus of the solitary tract. Appetite 2017; 113:231-238. [PMID: 28259536 DOI: 10.1016/j.appet.2017.02.040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Revised: 02/21/2017] [Accepted: 02/27/2017] [Indexed: 02/06/2023]
Abstract
Sensory information from the upper gastrointestinal tract is critical in food intake regulation. Signals from different levels of the digestive system are processed to the brain, among other systems, via the vagus nerve, which mainly projects towards the nucleus of the solitary tract (NST). The objective of this study was to analyze the participation of the gelatinous part (SolG) of the NST in short-term food intake. One-third of the stomach food content was withdrawn at 5 min after the end of a meal, and food was then available ad libitum for different time periods. SolG-lesioned and control animals ingested a similar amount of the initial liquid meal, but the former consumed significantly smaller amounts and failed to compensate for the food deficit, whereas the controls re-ingested virtually the same amount as extracted. These data suggest that the SolG, as in the case of related anatomical structures such as the vagus nerve or external lateral parabrachial subnucleus, may be relevant in particular circumstances that require the rapid processing of vagal-related food intake adjustment associated to the upper gastrointestinal tract.
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Affiliation(s)
- María A Zafra
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain; Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Campus de Cartuja, Granada 18071, Spain.
| | - Antonio D Agüera
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain
| | - Filomena Molina
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain; Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Campus de Cartuja, Granada 18071, Spain
| | - Amadeo Puerto
- Department of Psychobiology, University of Granada, Campus de Cartuja, Granada 18071, Spain; Mind, Brain, and Behavior Research Center (CIMCYC), University of Granada, Campus de Cartuja, Granada 18071, Spain
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Hurtado MM, García R, Puerto A. Tiapride prevents the aversive but not the rewarding effect induced by parabrachial electrical stimulation in a place preference task. Acta Neurobiol Exp (Wars) 2017. [DOI: 10.21307/ane-2017-057] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Naloxone blocks the aversive effects of electrical stimulation of the parabrachial complex in a place discrimination task. Neurobiol Learn Mem 2016; 136:21-27. [DOI: 10.1016/j.nlm.2016.09.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 09/12/2016] [Accepted: 09/18/2016] [Indexed: 01/02/2023]
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Hurtado MM, Puerto A. Tolerance to repeated rewarding electrical stimulation of the parabrachial complex. Behav Brain Res 2016; 312:14-9. [PMID: 27283973 DOI: 10.1016/j.bbr.2016.06.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Revised: 05/29/2016] [Accepted: 06/02/2016] [Indexed: 12/29/2022]
Abstract
The parabrachial complex has been related to various rewarding behavioral processes. As previously shown, electrical stimulation of the lateral parabrachial external (LPBe) subnucleus induces opiate-dependent concurrent place preference. In this study, two groups of animals (and their respective controls) were subjected to sessions of rewarding brain stimulation daily or on alternate days. The rats stimulated every other day maintained a consistent preference for the place associated with the brain stimulation. However, as also found in the Insular Cortex, there was a progressive decay in the initial place preference of animals receiving daily stimulation. These data suggest that the rewarding effects induced by electrical stimulation of LPBe subnucleus may be subject to tolerance. These findings are discussed with respect to other anatomical areas showing reward decay and to the reinforcing effects induced by various electrical and chemical rewarding agents.
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Affiliation(s)
- María M Hurtado
- Department of Psychobiology & Mind, Brain and Behavior Research Center (CIMCYC), Campus of Cartuja, University of Granada, Granada 18071, Spain.
| | - Amadeo Puerto
- Department of Psychobiology & Mind, Brain and Behavior Research Center (CIMCYC), Campus of Cartuja, University of Granada, Granada 18071, Spain
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Satiation and re-intake after partial withdrawal of gastric food contents: A dissociation effect in external lateral parabrachial lesioned rats. Brain Res Bull 2016; 127:126-133. [DOI: 10.1016/j.brainresbull.2016.09.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 09/06/2016] [Accepted: 09/09/2016] [Indexed: 11/19/2022]
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Differential effects of naloxone on rewarding electrical stimulation of the central nucleus of the amygdala and parabrachial complex in a place preference study. Brain Res Bull 2016; 124:182-9. [PMID: 27173444 DOI: 10.1016/j.brainresbull.2016.04.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 04/11/2016] [Accepted: 04/28/2016] [Indexed: 12/29/2022]
Abstract
The central nucleus of the amygdala (CeA) is considered to be involved in different affective, sensory, regulatory, and acquisition processes. This study analyzed whether electrical stimulation of the PB-CeA system induces preferences in a concurrent place preference (cPP) task, as observed after stimulation of the parabrachial-insular cortex (PB-IC) axis. It also examined whether the rewarding effects are naloxone-dependent. The results show that electrical stimulation of the CeA and external lateral parabrachial subnucleus (LPBe) induces consistent preference behaviors in a cPP task. However, subcutaneous administration of an opiate antagonist (naloxone; 4mg/ml/kg) blocked the rewarding effect of the parabrachial stimulation but not that of the amygdala stimulation. These results are interpreted in the context of multiple brain reward systems that appear to differ both anatomically and neurochemically, notably with respect to the opiate system.
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Kwak Y, Han J, Rhyu MR, Nam TS, Leem JW, Lee BH. Different spatial expressions of c-Fos in the nucleus of the solitary tract following taste stimulation with sodium, potassium, and ammonium ions in rats. J Neurosci Res 2014; 93:340-9. [PMID: 25243715 DOI: 10.1002/jnr.23485] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Revised: 08/29/2014] [Accepted: 09/02/2014] [Indexed: 11/10/2022]
Abstract
Cation-specific epithelial receptors on the tongue have been well demonstrated. However, active regions along the nucleus of the solitary tract (NST) for cations Na(+), K(+), NH4(+) are still unclear, even though the best responses of NST neurons to taste stimuli vary depending on the cell. In the present study, the spatial distribution patterns of cation-specific active regions in the NST are investigated. The tongues of urethane-anesthetized Sprague-Dawley rats (n = 25) were stimulated with artificial saliva (control), 0.5 M NaCl, 1.0 M NaCl, 0.5 M KCl, and 0.3 M NH(4) Cl. Then, the three-dimensional positions of c-Fos-like-immunoreactive (cFLI) cells in the NST were generated. The spatial distributions of cFLI cells in the NST were compared among five taste stimulations. cFLI cells were observed throughout the NST, irrespective of the stimulus; however, the intermediate-medial central regions of the NST had higher numbers of cFLI cells than the other regions in all taste stimulations. Analysis of images revealed that the activated regions in the NST differed significantly depending on the cations. The intermediate-dorsal-central region and the caudal-ventral region were activated by a 0.5 M concentration of sodium, the rostral-ventral region and the intermediate-dorsal/ventral region were activated by a 1.0 M concentration of sodium, the intermediate-dorsal/ventral region was activated by potassium ions, and the rostral-ventral region and the intermediate-ventral central region were activated by ammonium ions. These results suggest that the responses of NST cells to cation salt ions are regulated differentially.
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Affiliation(s)
- Yongho Kwak
- Department of Physiology, Yonsei University College of Medicine, Seoul, Korea
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Jiang E, Yu D, Feng Z. Subdiaphragmatic vagotomy reduces intake of sweet-tasting solutions in rats. Neural Regen Res 2014; 8:1560-7. [PMID: 25206451 PMCID: PMC4145969 DOI: 10.3969/j.issn.1673-5374.2013.17.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Accepted: 05/04/2013] [Indexed: 11/18/2022] Open
Abstract
Studies have shown that there are strong interactions between gustatory and visceral sensations in the central nervous system when rats ingest sweet foods or solutions. To investigate the role of the subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats deprived of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water.
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Affiliation(s)
- Enshe Jiang
- Institute of Public Hygiene, School of Nursing, Henan University, Kaifeng 475004, Henan Province, China
| | - Dongming Yu
- Department of Anatomy, Medical College of Henan University, Kaifeng 475004, Henan Province, China
| | - Zhifen Feng
- Institute of Public Hygiene, School of Nursing, Henan University, Kaifeng 475004, Henan Province, China
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Tsurugizawa T, Uneyama H. Differences in BOLD responses to intragastrically infused glucose and saccharin in rats. Chem Senses 2014; 39:683-91. [PMID: 25179231 DOI: 10.1093/chemse/bju040] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
The postingestive effect is different between caloric and noncaloric sweeteners. The gut administration of glucose induces a preference for flavored water which is paired with the intragastric infusion of glucose. However, a comparison of the brain response to the gut glucose and saccharin stimuli still remains to be demonstrated. Here, using functional magnetic resonance imaging, we investigated the blood oxygenation level-dependent signal response to gut glucose and saccharin in the brain of conscious rats. Glucose induced a positive signal increase in the amygdala and nucleus accumben, both of which receive dopaminergic input from the ventral tegmental area. In contrast, saccharin administration did not activate these areas. Both glucose and saccharin increased the blood oxygenation level-dependent signal intensity in the insular cortex and the nucleus of the solitary tract. These results show that there were significant differences between postingestive glucose and saccharin-induced increases in the blood oxygenation level-dependent signal in rats. Together with previous findings, these results suggest distinct activation patterns in the brain for both glucose and saccharin, which is partially due to different changes of internal signals, including the blood glucose and insulin levels.
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Affiliation(s)
- Tomokazu Tsurugizawa
- Institute for Innovation, Ajinomoto Co., Inc., Suzuki-cho 1-1, Kawasaki-ku, Kawasaki 210-8601, Japan Present address: CEA/DSV/I2BM/NeuroSpin, Bât 145, Point Courrier 156, 91191 Gif-sur-Yvette, France
| | - Hisayuki Uneyama
- Institute for Innovation, Ajinomoto Co., Inc., Suzuki-cho 1-1, Kawasaki-ku, Kawasaki 210-8601, Japan
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18
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Tokita K, Armstrong WE, St John SJ, Boughter JD. Activation of lateral hypothalamus-projecting parabrachial neurons by intraorally delivered gustatory stimuli. Front Neural Circuits 2014; 8:86. [PMID: 25120438 PMCID: PMC4114292 DOI: 10.3389/fncir.2014.00086] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 07/04/2014] [Indexed: 11/13/2022] Open
Abstract
The present study investigated a subpopulation of neurons in the mouse parabrachial nucleus (PbN), a gustatory and visceral relay area in the brainstem, that project to the lateral hypothalamus (LH). We made injections of the retrograde tracer Fluorogold (FG) into LH, resulting in fluorescent labeling of neurons located in different regions of the PbN. Mice were stimulated through an intraoral cannula with one of seven different taste stimuli, and PbN sections were processed for immunohistochemical detection of the immediate early gene c-Fos, which labels activated neurons. LH projection neurons were found in all PbN subnuclei, but in greater concentration in lateral subnuclei, including the dorsal lateral subnucleus (dl). Fos-like immunoreactivity (FLI) was observed in the PbN in a stimulus-dependent pattern, with the greatest differentiation between intraoral stimulation with sweet (0.5 M sucrose) and bitter (0.003 M quinine) compounds. In particular, sweet and umami-tasting stimuli evoked robust FLI in cells in the dl, whereas quinine evoked almost no FLI in cells in this subnucleus. Double-labeled cells were also found in the greatest quantity in the dl. Overall, these results support the hypothesis that the dl contains direct a projection to the LH that is activated preferentially by appetitive compounds; this projection may be mediated by taste and/or postingestive mechanisms.
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Affiliation(s)
- Kenichi Tokita
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center Memphis, TN, USA
| | - William E Armstrong
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center Memphis, TN, USA
| | | | - John D Boughter
- Department of Anatomy and Neurobiology, University of Tennessee Health Science Center Memphis, TN, USA
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19
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Yates BJ, Catanzaro MF, Miller DJ, McCall AA. Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness. Exp Brain Res 2014; 232:2455-69. [PMID: 24736862 DOI: 10.1007/s00221-014-3937-6] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 03/25/2014] [Indexed: 12/23/2022]
Abstract
Vomiting and nausea can be elicited by a variety of stimuli, although there is considerable evidence that the same brainstem areas mediate these responses despite the triggering mechanism. A variety of experimental approaches showed that nucleus tractus solitarius, the dorsolateral reticular formation of the caudal medulla (lateral tegmental field), and the parabrachial nucleus play key roles in integrating signals that trigger nausea and vomiting. These brainstem areas presumably coordinate the contractions of the diaphragm and abdominal muscles that result in vomiting. However, it is unclear whether these regions also mediate the autonomic responses that precede and accompany vomiting, including alterations in gastrointestinal activity, sweating, and changes in blood flow to the skin. Recent studies showed that delivery of an emetic compound to the gastrointestinal system affects the processing of vestibular inputs in the lateral tegmental field and parabrachial nucleus, potentially altering susceptibility for vestibular-elicited vomiting. Findings from these studies suggested that multiple emetic inputs converge on the same brainstem neurons, such that delivery of one emetic stimulus affects the processing of another emetic signal. Despite the advances in understanding the neurobiology of nausea and vomiting, much is left to be learned. Additional neurophysiologic studies, particularly those conducted in conscious animals, will be crucial to discern the integrative processes in the brain stem that result in emesis.
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Affiliation(s)
- Bill J Yates
- Department of Otolaryngology, Eye and Ear Institute, University of Pittsburgh, Room 519, Pittsburgh, PA, 15213, USA,
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20
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García R, Simon MJ, Puerto A. Rewarding effects of the electrical stimulation of the parabrachial complex: taste or place preference? Neurobiol Learn Mem 2013; 107:101-7. [PMID: 24291574 DOI: 10.1016/j.nlm.2013.11.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 11/05/2013] [Accepted: 11/18/2013] [Indexed: 11/24/2022]
Abstract
The lateral parabrachial complex has been related to various emotional-affective processes. It has been shown that electrical stimulation of the external Lateral Parabrachial (LPBe) nucleus can induce reinforcing effects in place preference and taste discrimination tasks but does not appear to support self-stimulation. This study examined the relative relevance of place and taste stimuli after electrical stimulation of the LPBe nucleus. A learning discrimination task was conducted that simultaneously included both sensory indexes (taste and place) in order to determine the preference of animals for one or the other. After a taste stimulus reversal task, the rewarding effect of stimulation was found to be preferentially associated with place. These results are discussed in the context of the rewarding action and biological constraints induced by different natural and artificial reinforcing agents.
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Affiliation(s)
- Raquel García
- Department of Psychobiology, University of Granada, Campus of Cartuja, Granada 18071, Spain.
| | - Maria J Simon
- Department of Psychobiology, University of Granada, Campus of Cartuja, Granada 18071, Spain
| | - Amadeo Puerto
- Department of Psychobiology, University of Granada, Campus of Cartuja, Granada 18071, Spain
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21
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Zafra MA, Simón MJ, Molina F, Puerto A. Lesions of the lateral parabrachial area block the aversive component and induced-flavor preference for the delayed intragastric administration of nutrients in rats: Effects on subsequent food and water intake. Nutr Neurosci 2013; 8:297-307. [PMID: 16669600 DOI: 10.1080/10284150600576655] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
The aim of this study was to examine the function of the lateral parabrachial area (LPB) in relation to the intragastric administration of nutrients. The consumption of flavors associated with intragastric nutrient administration and the subsequent food and water intake were measured in rats with lesions in the LPB. The results showed that bilateral LPB lesions prevented development of aversions and induced flavor preference when there was a delay between the presentation of a flavor and the intragastric administration of nutrients. However, these lesions did not disrupt development of the aversive process when there was no delay between the presentations. Likewise, the LPB lesions increased subsequent food intake when there was a delay but not when there was no delay between the presentations. In contrast, the water intake was reduced in both situations. These results are interpreted in terms of a dual visceral system for processing the intragastric effects of foods.
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Affiliation(s)
- María A Zafra
- Psychobiology Area, University of Granada, Campus de Cartuja, Granada 18071, Spain.
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22
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Neural Mechanisms That Underlie Angina-Induced Referred Pain in the Trigeminal Nerve Territory: A c-Fos Study in Rats. ISRN PAIN 2013; 2013:671503. [PMID: 27335881 PMCID: PMC4893399 DOI: 10.1155/2013/671503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Accepted: 07/08/2013] [Indexed: 11/17/2022]
Abstract
The present study was designed to determine whether the trigeminal sensory nuclear complex (TSNC) is involved in angina-induced referred pain in the trigeminal nerve territory and to identify the peripheral nerve conducting nociceptive signals that are input into the TSNC. Following application of the pain producing substance (PPS) infusion, the number of Fos-labeled cells increased significantly in the subnucleus caudalis (Sp5C) compared with other nuclei in the TSNC. The Fos-labeled cells in the Sp5C disappeared when the left and right cervical vagus nerves were sectioned. Lesion of the C1-C2 spinal segments did not reduce the number of Fos-labeled cells. These results suggest that the nociceptive signals that conduct vagal afferent fibers from the cardiac region are input into the Sp5C and then projected to the thalamus.
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23
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Wang Q, Li J, Yang X, Chen K, Sun B, Yan J. Inhibitory effect of activation of GABAA receptor in the central nucleus of amygdala on the sodium intake in the sodium-depleted rat. Neuroscience 2012; 223:277-84. [DOI: 10.1016/j.neuroscience.2012.07.068] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2012] [Revised: 07/04/2012] [Accepted: 07/31/2012] [Indexed: 10/28/2022]
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24
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Brainstem sensing of meal-related signals in energy homeostasis. Neuropharmacology 2012; 63:31-45. [DOI: 10.1016/j.neuropharm.2012.03.019] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 03/12/2012] [Accepted: 03/23/2012] [Indexed: 11/15/2022]
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25
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Torii K, Uematsu A, Tsurugizawa T. Brain Response to the Luminal Nutrient Stimulation. CHEMOSENS PERCEPT 2012. [DOI: 10.1007/s12078-011-9113-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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26
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Kwak Y, Rhyu MR, Bai SJ, Sa YH, Kwon MJ, Lee BH. c-Fos Expression in the Nucleus of the Solitary Tract in Response to Salt Stimulation in Rats. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2011; 15:437-43. [PMID: 22359483 PMCID: PMC3282233 DOI: 10.4196/kjpp.2011.15.6.437] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2011] [Revised: 12/17/2011] [Accepted: 12/20/2011] [Indexed: 01/19/2023]
Abstract
Salt signals in tongue are relayed to the nucleus of the solitary tract (NST). This signaling is very important to determine whether to swallow salt-related nutrition or not and suggests some implications in discrimination of salt concentration. Salt concentration-dependent electrical responses in the chorda tympani and the NST were well reported. But salt concentration-dependency and spatial distribution of c-Fos in the NST were not well established. In the present study, NaCl signaling in the NST was studied in urethane-anesthetized rats. The c-Fos immunoreactivity in the six different NST areas along the rostral-caudal axis and six subregions in each of bilateral NST were compared between applications of distilled water and different concentrations of NaCl to the tongue of experimental animals. From this study, salt stimulation with high concentration (1.0 M NaCl) induced significantly higher c-Fos expression in intermediate NST and dorsal-medial and dorsal-middle subregions of the NST compared to distilled water stimulation. The result represents the specific spatial distribution of salt taste perception in the NST.
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Affiliation(s)
- Yongho Kwak
- Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Korea
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27
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Simon MJ, Garcia R, Puerto A. Concurrent stimulation-induced place preference in lateral hypothalamus and parabrachial complex: Differential effects of naloxone. Behav Brain Res 2011; 225:311-6. [DOI: 10.1016/j.bbr.2011.07.029] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 07/12/2011] [Accepted: 07/17/2011] [Indexed: 12/01/2022]
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28
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Chen K, Yan J, Li J, Lv B, Zhao X. c-Fos expression in rat brainstem following intake of sucrose or saccharin. Front Med 2011; 5:294-301. [PMID: 21964712 DOI: 10.1007/s11684-011-0144-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2011] [Accepted: 06/10/2011] [Indexed: 11/28/2022]
Abstract
To examine whether the activation of brainstem neurons during intake of a sweet tastant is due to orosensory signals or post-ingestive factors, we compared the distribution of c-Fos-like immunoreactivity (c-FLI) in the nucleus of the solitary tract (NST) and parabrachial nucleus (PBN) of brainstem following ingestion of 0.25 Msucrose or 0.005 M saccharin solutions. Immunopositive neurons were localized mainly in the middle zone of the PBN and four rostral-caudal subregions of the NST. Intake of sucrose increased the number of FLI neurons in almost every subnucleus of the PBN (F((2,13)) = 7.610, P = 0.023), in addition to the caudal NST at the level of the area postrema (F((2,13)) = 10.777, P = 0.003) and the NST intermediate zone (F((2,13)) = 7.193, P = 0.014). No significant increase in the number of c-Fos positive neurons was detected in response to saccharin ingestion, although there was a trend towards a modest increase in a few select NST and PBN nuclei. These results suggest that the PBN and NST may be involved in sweet taste perception and modulation of sweet tastant intake, but the significantly enhanced intensity of Fos expression induced by sucrose indicates that PBN/NST neuronal activity is driven by the integrated effects of sweet taste sensation and post-ingestive signals.
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Affiliation(s)
- Ke Chen
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China
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29
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Tsurugizawa T, Uematsu A, Uneyama H, Torii K. Different BOLD responses to intragastric load of L-glutamate and inosine monophosphate in conscious rats. Chem Senses 2010; 36:169-76. [PMID: 20956735 DOI: 10.1093/chemse/bjq107] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
In this study, we compared the blood oxygen level-dependent (BOLD) signal changes between intragastric load of monosodium L-glutamate (MSG) and inosine monophosphate (IMP), which elicit the umami taste. An intragastric load of 30 mM IMP or 60 mM MSG induced a BOLD signal increase in several brain regions, including the nucleus of the solitary tract (NTS), lateral hypothalamus (LH), and insular cortex. Only MSG increased the BOLD signal in the amygdala (AMG). The time course of the BOLD signal changes in the NTS and the LH in the IMP group was different from that of the MSG group. We further compared the brain regions correlated with the BOLD signal change in the NTS between MSG and IMP groups. The BOLD responses in the hippocampus and the orbital cortex were associated with activation of the NTS in both MSG and IMP groups, but the association in the AMG and the pyriform was only in MSG group. These results indicate that gut stimulation with MSG and IMP evoked BOLD responses in distinct regions with different temporal patterns and that the mechanism of perception of L-glutamate and IMP in the gastrointestinal tract differed from that in the taste-sensing system.
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Affiliation(s)
- Tomokazu Tsurugizawa
- Institute of Life Sciences, Ajinomoto Co., Inc., Suzuki-cho 1-1, Kawasaki-ku, Kawasaki 210-8601, Japan
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30
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Geerling JC, Shin JW, Chimenti PC, Loewy AD. Paraventricular hypothalamic nucleus: axonal projections to the brainstem. J Comp Neurol 2010; 518:1460-99. [PMID: 20187136 DOI: 10.1002/cne.22283] [Citation(s) in RCA: 209] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The paraventricular hypothalamic nucleus (PVH) contains many neurons that innervate the brainstem, but information regarding their target sites remains incomplete. Here we labeled neurons in the rat PVH with an anterograde axonal tracer, Phaseolus vulgaris leucoagglutinin (PHAL), and studied their descending projections in reference to specific neuronal subpopulations throughout the brainstem. While many of their target sites were identified previously, numerous new observations were made. Major findings include: 1) In the midbrain, the PVH projects lightly to the ventral tegmental area, Edinger-Westphal nucleus, ventrolateral periaqueductal gray matter, reticular formation, pedunculopontine tegmental nucleus, and dorsal raphe nucleus. 2) In the dorsal pons, the PVH projects heavily to the pre-locus coeruleus, yet very little to the catecholamine neurons in the locus coeruleus, and selectively targets the viscerosensory subregions of the parabrachial nucleus. 3) In the ventral medulla, the superior salivatory nucleus, retrotrapezoid nucleus, compact and external formations of the nucleus ambiguous, A1 and caudal C1 catecholamine neurons, and caudal pressor area receive dense axonal projections, generally exceeding the PVH projection to the rostral C1 region. 4) The medial nucleus of the solitary tract (including A2 noradrenergic and aldosterone-sensitive neurons) receives the most extensive projections of the PVH, substantially more than the dorsal vagal nucleus or area postrema. Our findings suggest that the PVH may modulate a range of homeostatic functions, including cerebral and ocular blood flow, corneal and nasal hydration, ingestive behavior, sodium intake, and glucose metabolism, as well as cardiovascular, gastrointestinal, and respiratory activities.
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Affiliation(s)
- Joel C Geerling
- Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
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31
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Uematsu A, Tsurugizawa T, Uneyama H, Torii K. Brain-gut communication via vagus nerve modulates conditioned flavor preference. Eur J Neurosci 2010; 31:1136-43. [DOI: 10.1111/j.1460-9568.2010.07136.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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32
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Simon MJ, Molina F, Puerto A. Conditioned place preference but not rewarding self-stimulation after electrical activation of the external lateral parabrachial nucleus. Behav Brain Res 2009; 205:443-9. [DOI: 10.1016/j.bbr.2009.07.028] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2009] [Revised: 07/21/2009] [Accepted: 07/26/2009] [Indexed: 11/27/2022]
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33
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Tsurugizawa T, Uematsu A, Uneyama H, Torii K. Effects of isoflurane and alpha-chloralose anesthesia on BOLD fMRI responses to ingested L-glutamate in rats. Neuroscience 2009; 165:244-51. [PMID: 19819307 DOI: 10.1016/j.neuroscience.2009.10.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2009] [Revised: 09/10/2009] [Accepted: 10/03/2009] [Indexed: 11/30/2022]
Abstract
It is important to investigate the effect of anesthesia on blood oxygenation level-dependent (BOLD) signals in an animal model. Many researchers have investigated the BOLD response to visual, sensory, and chemical stimuli in anesthetized rats. There are no reports, however, comparing the differences in the BOLD signal change between anesthetized and conscious rats when a visceral nutrient signal arises. Here, using functional magnetic resonance imaging (fMRI), we investigated the differences in the BOLD signal changes after intragastric administration of l-glutamate (Glu) under three anesthesia conditions: conscious, alpha-chloralose-anesthetized, and isoflurane-anesthetized condition. Under the conscious and alpha-chloralose condition, we observed the significant BOLD signal increase in the medial prefrontal cortex (mPFC), insular cortex (IC), hippocampus, and several hypothalamic regions including the lateral and ventromedial nucleus. In chloralose group, however, gut Glu stimulation induced BOLD signal increase in the prelimbic cortex and orbital cortex, which did not activate in conscious condition. Meanwhile, under isoflurane-anesthetized condition, we did not observe the BOLD signal increase in these areas. BOLD signal intensity in the nucleus of the solitary tract (NTS), to which vagus nerve transmits the visceral information from the gastrointestinal tract, increased in all conditions. Importantly, under conscious condition, we observed increased BOLD signal intensity in several regions related to the metabolic state (i.e. hunger or satiety), such as the mPFC, ventromedial and lateral hypothalamus (LH). Our results suggest that alpha-chloralose and isoflurane anesthesia caused distinct effects on BOLD response to the gut l-Glu stimulation in several brain regions.
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Affiliation(s)
- T Tsurugizawa
- Institute of Life Sciences, Ajinomoto, Co., Inc., Kawasaki, Japan
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34
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Hashimoto K, Obata K, Ogawa H. Characterization of parabrachial subnuclei in mice with regard to salt tastants: possible independence of taste relay from visceral processing. Chem Senses 2009; 34:253-67. [PMID: 19179538 DOI: 10.1093/chemse/bjn085] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
We examined whether salt taste and/or abdominal illness were dealt within different subnuclei in the parabrachial nucleus (PBN) in mice, using retrograde tracing methods and c-Fos-like immunoreactivity (FLI) detection procedures. Some PBN subnuclei have distinct functions and receive various sensory inputs from the nucleus of the solitary tract (NTS) and other areas and relay them to the higher order nuclei such as the thalamus. The afferent-dependent pattern of FLI has been investigated in the PBN. However, it is unclear in which PBN subnuclei the tastants induce c-Fos, or whether PBN subnuclei process taste inputs separately from other inputs, or integrate them. After the tracer injections into the thalamic taste relay, the retrograde labeled cells revealed the taste relay cells in the PBN at the boundary with the superior cerebellar peduncle of both the inner part of the external lateral subnucleus and the medial subnucleus and in the waist area. On the other hand, NaCl intake induced intense FLI in the dorsal lateral subnucleus, whereas LiCl intake yielded intense FLI in both the dorsal lateral subnucleus and the outer part of the external lateral subnucleus. Thus, the present findings that subnuclei relaying taste information to the thalamus do not yield FLI in response to salt taste and abdominal illness indicate that they lack FLI yielding pathways or that they are independent from the subnuclei processing salt taste and visceral information via c-Fos in mice.
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Affiliation(s)
- Koji Hashimoto
- Department of Medical Laboratory Sciences, School of Health Sciences, Kumamoto University, Kuhonji 4-24-1, Kumamoto 862-0976, Japan.
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35
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De la Torre ML, Agüero Á. The role of the medial-external subnucleus of the medial parabrachial nucleus in hypertonic NaCl-induced concurrent and delayed-sequential flavor avoidance learning. Exp Brain Res 2009; 194:207-18. [DOI: 10.1007/s00221-008-1686-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2008] [Accepted: 12/06/2008] [Indexed: 10/21/2022]
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36
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Mitome M, Low HP, Lora Rodriguez KM, Kitamoto M, Kitamura T, Schwartz WJ. Neuronal differentiation of EGF-propagated neurosphere cells after engraftment to the nucleus of the solitary tract. Neurosci Lett 2008; 444:250-3. [PMID: 18761057 DOI: 10.1016/j.neulet.2008.08.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2008] [Revised: 08/15/2008] [Accepted: 08/16/2008] [Indexed: 11/30/2022]
Abstract
Neural precursor cells expanded with epidermal growth factor (EGF) exhibit multipotentiality in vitro, but they differentiate predominantly as glial phenotypes after their transplantation in vivo. Here we demonstrate that EGF-propagated precursors from the murine striatal subventricular zone can exhibit robust incorporation and neuronal differentiation within the nucleus of the solitary tract (NST) after injection into the cisterna magna of neonatal or young adult mice. About two-third of engrafted cells appeared NeuN positive in the region of the gelatinous subnucleus, a region notable for its lack of myelinated fibers. The NST may provide a useful model for understanding the physiological and metabolic regulation of postnatal neurogenesis.
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Affiliation(s)
- Masato Mitome
- Department of Pediatric Dentistry, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
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37
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Knauf C, Cani PD, Kim DH, Iglesias MA, Chabo C, Waget A, Colom A, Rastrelli S, Delzenne NM, Drucker DJ, Seeley RJ, Burcelin R. Role of central nervous system glucagon-like Peptide-1 receptors in enteric glucose sensing. Diabetes 2008; 57:2603-12. [PMID: 18519802 PMCID: PMC2551668 DOI: 10.2337/db07-1788] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2007] [Accepted: 05/28/2008] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Ingested glucose is detected by specialized sensors in the enteric/hepatoportal vein, which send neural signals to the brain, which in turn regulates key peripheral tissues. Hence, impairment in the control of enteric-neural glucose sensing could contribute to disordered glucose homeostasis. The aim of this study was to determine the cells in the brain targeted by the activation of the enteric glucose-sensing system. RESEARCH DESIGN AND METHODS We selectively activated the axis in mice using a low-rate intragastric glucose infusion in wild-type and glucagon-like peptide-1 (GLP-1) receptor knockout mice, neuropeptide Y-and proopiomelanocortin-green fluorescent protein-expressing mice, and high-fat diet diabetic mice. We quantified the whole-body glucose utilization rate and the pattern of c-Fos positive in the brain. RESULTS Enteric glucose increased muscle glycogen synthesis by 30% and regulates c-Fos expression in the brainstem and the hypothalamus. Moreover, the synthesis of muscle glycogen was diminished after central infusion of the GLP-1 receptor (GLP-1Rc) antagonist Exendin 9-39 and abolished in GLP-1Rc knockout mice. Gut-glucose-sensitive c-Fos-positive cells of the arcuate nucleus colocalized with neuropeptide Y-positive neurons but not with proopiomelanocortin-positive neurons. Furthermore, high-fat feeding prevented the enteric activation of c-Fos expression. CONCLUSIONS We conclude that the gut-glucose sensor modulates peripheral glucose metabolism through a nutrient-sensitive mechanism, which requires brain GLP-1Rc signaling and is impaired during diabetes.
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Affiliation(s)
- Claude Knauf
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
| | - Patrice D. Cani
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
- Unit of Pharmacokinetics, Metabolism, Nutrition, and Toxicology, Université Catholique de Louvain, Brussels, Belgium
| | - Dong-Hoon Kim
- Department of Psychiatry, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio
| | - Miguel A. Iglesias
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
| | - Chantal Chabo
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
| | - Aurélie Waget
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
| | - André Colom
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
| | - Sophie Rastrelli
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
| | - Nathalie M. Delzenne
- Unit of Pharmacokinetics, Metabolism, Nutrition, and Toxicology, Université Catholique de Louvain, Brussels, Belgium
| | - Daniel J. Drucker
- Banting and Best Diabetes Centre, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, Canada
| | - Randy J. Seeley
- Department of Psychiatry, Genome Research Institute, University of Cincinnati, Cincinnati, Ohio
| | - Remy Burcelin
- Institut de Medecine Moleculaire de Rangueil, Institut National de la Santé et de la Recherche Médicale U858, IFR31, Centre Hospitalier Universitaire Rangueil, Toulouse, France
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Simon MJ, Zafra MA, Molina F, Puerto A. Consistent rewarding or aversive effects of the electrical stimulation of the lateral parabrachial complex. Behav Brain Res 2008; 190:67-73. [DOI: 10.1016/j.bbr.2008.02.036] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2007] [Revised: 01/31/2008] [Accepted: 02/04/2008] [Indexed: 12/28/2022]
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Abstract
Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature in mammals and birds during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. The primary sources of neurally regulated metabolic heat production are mitochondrial oxidation in brown adipose tissue, increases in heart rate and shivering in skeletal muscle. Thermogenesis is regulated in each of these tissues by parallel networks in the central nervous system, which respond to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate the appropriate sympathetic and somatic efferents. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates thermogenesis and discusses the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E(2), to increase body temperature. The cold thermal afferent circuit from cutaneous thermal receptors ascends via second-order thermosensory neurons in the dorsal horn of the spinal cord to activate neurons in the lateral parabrachial nucleus, which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus and possibly of sympathetic and somatic premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, activates excitatory inputs to spinal sympathetic and somatic motor circuits to drive thermogenesis.
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Affiliation(s)
- Shaun F Morrison
- Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
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Wan S, Browning KN. D-glucose modulates synaptic transmission from the central terminals of vagal afferent fibers. Am J Physiol Gastrointest Liver Physiol 2008; 294:G757-63. [PMID: 18202107 DOI: 10.1152/ajpgi.00576.2007] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Experimental evidence suggests that glucose modulates gastric functions via vagally mediated effects. It is unclear whether glucose affects only peripheral vagal nerve activity or whether glucose also modulates vagal circuitry at the level of the brain stem. This study used whole cell patch-clamp recordings from neurons of the nucleus of the tractus solitarius (NTS) to assess whether acute variations in glucose modulates vagal brain stem neurocircuitry. Increasing D-glucose concentration induced a postsynaptic response in 40% of neurons; neither the response type (inward vs. outward current) nor response magnitude was altered in the presence of tetrodotoxin suggesting direct effects on the NTS neuronal membrane. In contrast, reducing d-glucose concentration induced a postsynaptic response (inward or outward current) in 54% of NTS neurons; tetrodotoxin abolished these responses, suggesting indirect sites of action. The frequency, but not amplitude, of spontaneous and miniature excitatory postsynaptic currents (EPSCs) was correlated with d-glucose concentration in 79% of neurons tested (n = 48). Prior surgical afferent rhizotomy abolished the ability of D-glucose to modulate spontaneous EPSC frequency, suggesting presynaptic actions at vagal afferent nerve terminals to modulate glutamatergic synaptic transmission. In experiments in which EPSCs were evoked via electrical stimulation of the tractus solitarius, EPSC amplitude correlated with D-glucose concentration. These effects were not mimicked by L-glucose, suggesting the involvement of glucose metabolism, not uptake, in the nerve terminal. These data suggest that the synaptic connections between vagal afferent nerve terminals and NTS neurons are a strong candidate for consideration as one of the sites where glucose-evoked changes in vagovagal reflexes occurs.
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Affiliation(s)
- Shuxia Wan
- Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
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41
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The role of the dorsal-most part of the lateral parabrachial nucleus in the processing of hypertonic NaCl using different conditioned flavor avoidance paradigms. Exp Brain Res 2008; 186:481-91. [PMID: 18193413 DOI: 10.1007/s00221-007-1250-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2007] [Accepted: 12/05/2007] [Indexed: 10/22/2022]
Abstract
The parabrachial nucleus (PBN) has been strongly associated with taste aversion learning (TAL) acquisition. Independent of its suggested associative functions, this brain stem centre plays a key role in the sensorial processing of both gustatory and visceral information. The sensory visceral functions have been attributed to the lateral area of the PBN (PBNl) but, recently, it has been proposed that within this area a form of anatomical and functional segregation may also exist, determined by factors such as, the learning paradigm used, the nature of aversive agent used, or the route chosen for the administration of this agent. This study used a lesion approach in rats to address the question of whether the dorsal most portion of the PBNl plays a key role in the acquisition of a conditioned avoidance to flavored stimuli induced by hypertonic sodium chloride (intra gastric), and whether this role is dependent on the flavor avoidance learning (FAL) paradigm used, concurrent (experiment 1) or delayed-sequential FAL (experiment 2). Results showed a clear disruptive effect of the PBNl electrolytic lesion on the acquisition of the concurrent FAL, but hardly any attenuation of the delayed-sequential FAL. This finding is discussed in the context of the hypothesis that two separate and apparently non-redundant routes exist for the processing of the visceral information.
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Simon MJ, Garcia R, Zafra MA, Molina F, Puerto A. Learned preferences induced by electrical stimulation of a food-related area of the parabrachial complex: Effects of naloxone. Neurobiol Learn Mem 2007; 87:332-42. [PMID: 17084647 DOI: 10.1016/j.nlm.2006.09.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2006] [Revised: 09/22/2006] [Accepted: 09/22/2006] [Indexed: 11/23/2022]
Abstract
Electrical stimulation of the External Lateral Parabrachial Subnucleus (LPBe), a food-related area, induced behavioral preferences for associated stimuli in a taste discrimination learning task. Although this stimulation appeared to be ineffective to elicit standard lever press self-stimulation, it induced place preference for one of two training compartments of a rectangular maze in which animals (adult male Wistar rats) received concurrent electrical brain stimulation. In subjects that consistently showed a preference behavior in different trials, administration of the opioid antagonist naloxone (4 mg/ml/kg) blocked concurrent learning when the test was made in a new maze but not in the same maze in which animals had learned the task. These results are discussed in terms of the possible participation of the LPBe subnucleus in different natural and artificial brain reward systems.
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Affiliation(s)
- Maria J Simon
- Psychobiology, University of Granada, Campus of Cartuja, Granada 18071, Spain.
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43
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44
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Ward HG, Simansky KJ. Chronic prevention of mu-opioid receptor (MOR) G-protein coupling in the pontine parabrachial nucleus persistently decreases consumption of standard but not palatable food. Psychopharmacology (Berl) 2006; 187:435-46. [PMID: 16847679 DOI: 10.1007/s00213-006-0463-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2006] [Accepted: 05/29/2006] [Indexed: 12/01/2022]
Abstract
RATIONALE Acute pharmacological studies implicate mu-opioid receptors (MORs) in the parabrachial nucleus (PBN) of the brainstem in modulating eating. The long-term effects of preventing the cellular function of parabrachial MORs on food consumption remain to be elucidated. OBJECTIVES To determine whether (1) chronic inhibition of MOR-mediated G-protein coupling in the PBN of rats would persistently reduce eating and (2) food properties dictate the effects of MOR blockade. MATERIALS AND METHODS We microinfused the irreversible MOR antagonist, beta-funaltrexamine (beta-FNA) into the lateral PBN and measured the intake of standard and calorically dense palatable chow for 1 week. First, rats were given standard chow for 20 h daily and a calorically dense palatable chow for 4 h during the day. We infused the agonist, [D: -Ala(2), N-Me-Phe(4), Glycinol(5)]-Enkephalin (DAMGO), 1 week after beta-FNA to probe the acute effects of exogenous stimulation of MORs on palatable food intake. [(35)S]GTPgammaS autoradiography quantified regional loss of MOR cellular function. Next, we measured the actions of beta-FNA on food intake in rats given only standard or palatable chow for 1 week. RESULTS One infusion of beta-FNA persistently decreased consumption of standard but not palatable chow, regardless of feeding regimen. beta-FNA also blocked DAMGO-stimulated palatable chow intake, prevented DAMGO-stimulated G-protein coupling in the central and external lateral subnuclei of the PBN, and decreased coupling in the medial PBN. beta-FNA did not affect kappa-opioid receptors. CONCLUSIONS MORs in the lateral PBN serve a physiological role in stimulating consumption of standard food. Properties of the diet, such as high palatability or caloric density, may override the influence of inhibiting MOR function.
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MESH Headings
- 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/pharmacology
- Analgesics, Non-Narcotic/pharmacology
- Analgesics, Opioid/pharmacology
- Animals
- Behavior, Animal/drug effects
- Circadian Rhythm
- Eating/drug effects
- Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
- Feeding Behavior/drug effects
- Food Preferences/drug effects
- GTP-Binding Proteins/metabolism
- Male
- Naltrexone/analogs & derivatives
- Naltrexone/pharmacology
- Narcotic Antagonists/pharmacology
- Pons/drug effects
- Pons/metabolism
- Rats
- Rats, Sprague-Dawley
- Receptors, G-Protein-Coupled/antagonists & inhibitors
- Receptors, Opioid, mu/antagonists & inhibitors
- Receptors, Opioid, mu/metabolism
- Time Factors
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Affiliation(s)
- Heather G Ward
- Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
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Richard S, Engblom D, Paues J, Mackerlova L, Blomqvist A. Activation of the parabrachio-amygdaloid pathway by immune challenge or spinal nociceptive input: a quantitative study in the rat using Fos immunohistochemistry and retrograde tract tracing. J Comp Neurol 2005; 481:210-9. [PMID: 15562506 DOI: 10.1002/cne.20384] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Peripheral nociceptive stimulation results in activation of neurons in the pontine parabrachial nucleus (PB) of rats. Electrophysiological studies have suggested that noxiously activated PB neurons project to the amygdala, constituting a potential pathway for emotional aspects of pain. In the present study we examined this hypothesis by combining retrograde tract tracing with Fos immunohistochemistry. Cholera toxin subunit B was injected into the amygdala of rats. After a minimum of 48 hours the rats were given a subcutaneous injection of 100 microl of 5% formalin into one hindpaw and killed 60-90 minutes later. A dense aggregation of retrogradely labeled neurons was seen in the external lateral PB. Fos-expressing neurons were present preferentially in the central, dorsal, and superior lateral subnuclei as well as in the lateral crescent area, as described previously. There was little overlap between the retrogradely labeled and Fos-expressing populations and double-labeled neurons were rare. In contrast, systemic immune challenge by intravenous injection of bacterial wall lipopolysaccharide resulted in a Fos expression that overlapped the retrograde labeling in the external lateral PB, and many double-labeled neurons were seen. While these data provide direct functional anatomical evidence that nociceptive information from the hindlimb is relayed to the amygdala via the parabrachial nucleus, the number of parabrachio-amygdaloid neurons involved is small. Considering the widespread activation of parabrachio-amygdaloid neurons by a variety of visceral and humoral stimuli, the parabrachio-amygdaloid pathway thus appears to be more involved in the mediation of information related to viscerally and humorally elicited activity than in transmission of spinal nociceptive inputs.
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Affiliation(s)
- Sabine Richard
- Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37 380 Nouzilly, France
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Abstract
Over 100 publications, principally from five groups, describe an effect of amylin and amylin analogs in inhibition of food intake in animals and humans. The major groups contributing to this area are those of the following: Chance and Balasubramaniam (Balasubramaniam et al., 1991a,b; Chance et al., 1991a,b, 1992a,b, 1993). Morley, Flood, and Edwards (Edwards and Morley, 1992; Flood and Morley, 1992; Macintosh et al., 2000; Morley and Flood, 1991, 1994; Morley et al., 1992, 1993, 1994, 1995, 1996, 1997). Lutz, Geary, and others (Barth et al., 2003; Del Prete et al., 2002; Lutz et al., 1994, 1995a,b, 1996a,b, 1997a,b, 1998a,b,c, 2000a,b, 2001a,b,c, 2003; Mollet et al., 2001, 2003a,b, 2004; Riediger et al., 2002, 2004; Rushing et al., 2000a,b, 2001, 2002). Workers at Amylin Pharmaceuticals Inc., or their collaborators (Bhavsar et al., 1995, 1996, 1997a, 1998; Birkemo et al., 1995; Chapman et al., 2004a,b; Edwards et al., 1998; Feinle et al., 2002; Mack et al., 2003; Riediger et al., 1999; Roth et al., 2004; Watkins et al., 1996; Weyer et al., 2004; Young, 1997; Young and Bhavsar, 1996). Arnelo, Reidelberger, and others (Arnelo et al., 1996a,b, 1997a,b, 1998, 2000; Fruin et al., 1997; Granqvist et al., 1997; Reidelberger et al., 2001, 2002, 2004). The magnitude of amylin inhibition of food intake, and its potency for this effect when delivered peripherally, suggests a physiological role in satiogenesis. Increases in food intake following disruption of amylin signal-signaling (e.g., with amylin receptor blockade, or with amylin gene knock-out mice) further support a role of endogenous amylin to tonically restrict nutrient intake. In addition, synergies with other endogenous satiety agents may be present, and convey greater physiological importance than is conveyed by single signals. The anorectic effect of amylin is consistent with a classic amylin pharmacology. The anorectic effect of peripheral amylin appears principally due to a direct action at the area postrema/nucleus tractus solitarius, and is not merely a consequence of gastric fullness, for example. Circulating amylin appears to physiologically inhibit secretion of ghrelin, an orexigenic peptide from the stomach. In contrast to the actions of many other anorexigens, amylin appears to stimulate drinking. This disposgenic effect is likely mediated via amylin-sensitive neurones in the subfornical organ, a circumventricular structure, that like the area postrema does not present a blood-brain barrier. Amylin's dipsogenic effect may explain prandial drinking, which has heretofore been regarded as a learned behavior.
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Affiliation(s)
- Andrew Young
- Amylin Pharmaceuticals, Inc., San Diego, California, USA
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Liu JH, Li J, Yan J, Chang XR, Cui RF, He JF, Hu JM. Expression of c-fos in the nucleus of the solitary tract following electroacupuncture at facial acupoints and gastric distension in rats. Neurosci Lett 2004; 366:215-9. [PMID: 15276250 DOI: 10.1016/j.neulet.2004.05.068] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2004] [Revised: 05/15/2004] [Accepted: 05/18/2004] [Indexed: 12/16/2022]
Abstract
Clinical practice has shown that acupuncture at facial acupoints has curative effects on some visceral diseases (especially gastrointestinal diseases). However, the physiological basis has not been clarified yet. In the present study, expression of c-fos in the nucleus of the solitary tract (NTS) of rats following gastric distension and electroacupuncture (EA) at Yangbai (GB14) and Sibai (ST2) as well as Jiache (ST6) acupoints was observed by using immunohistochemistry technique. After EA at the three facial acupoints, c-fos immunoreactive (c-fos-IR) neurons were mainly distributed in the medial (mNTS) and intermediate subnucleus of the NTS, and a few were scatteredly distributed in the dorsalmedial and commissural subnucleus of the NTS. Furthermore, there is difference in the number of c-fos-IR neurons in the mNTS following EA at the three facial acupoints. The number in the EA at ST2 and GB14 group is the highest and the lowest, respectively. Gastric distension induces obviously the expression of c-fos, which is mainly confined in the mNTS. The results suggest that the noxious visceral and somatic afferent information from the stomach and face may converge in the mNTS, which may be involved in the effect of EA at facial acupoints on the gastrointestinal pain.
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Affiliation(s)
- Jian-Hua Liu
- Department of Analysis and Measurement Science, Wuhan University, Wuhan 430072, PR China
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Shuai XW, Xie PY. Expression and localization of c-Fos and NOS in the central nerve system following esophageal acid stimulation in rats. World J Gastroenterol 2004; 10:2287-91. [PMID: 15259085 PMCID: PMC4724975 DOI: 10.3748/wjg.v10.i15.2287] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2004] [Revised: 01/03/2004] [Accepted: 02/09/2004] [Indexed: 12/15/2022] Open
Abstract
AIM To determine the distribution of neurons expressing c-Fos and nitric oxide synthase (NOS) in the central nerve system (CNS) following esophageal acid exposure, and to investigate the relationship between c-Fos and NOS. METHODS Twelve Wistar rats were randomly divided into two equal groups. Hydrochloric acid with pepsin was perfused in the lower part of the esophagus for 60 min. As a control, normal saline was used. Thirty minutes after the perfusion, the rats were killed and brains were removed and processed for c-Fos immunohistochemistry and NADPH-d histochemistry. Blood pressure (BP), heart rate (HR), and respiratory rate (RR) during the experimental procedures were recorded every 10 min. RESULTS There were no significant differences in BP, HR and RR between the two groups. c-Fos immunoreactivity was significantly increased in rats receiving acid plus pepsin perfusion in amygdala (AM), paraventricular nucleus (PVN), parabrachial nucleus (PBN), nucleus tractus solitarius and dorsal motor nucleus of vagus (NTS/DMV), nucleus ambiguous (NA), reticular nucleus of medulla (RNM) and area postrema (AP). NOS reactivity in this group was significantly increased in PVN, PBN, NTS/DMV, RNM and AP. c-Fos and NOS had significant correlation between PVN, PBN, NTS/DMV, RNM and AP. CONCLUSION Acid plus pepsin perfusion of the esophagus results in neural activation in areas of CNS, and NO is likely one of the neurotransmitters in some of these areas.
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Affiliation(s)
- Xiao-Wei Shuai
- Department of Gastroenterology, First Hospital of Peking University, Beijing 100034, China
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Mazda T, Yamamoto H, Fujimura M, Fujimiya M. Gastric distension-induced release of 5-HT stimulates c-fos expression in specific brain nuclei via 5-HT3 receptors in conscious rats. Am J Physiol Gastrointest Liver Physiol 2004; 287:G228-35. [PMID: 14684379 DOI: 10.1152/ajpgi.00373.2003] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
We examined c-fos expression in specific brain nuclei in response to gastric distension and investigated whether 5-HT released from enterochromaffin (EC) cells was involved in this response. The role of 5-HT3 receptors in this mechanism was also addressed. Release of 5-HT was examined in an ex vivo-perfused stomach model, whereas c-fos expression in brain nuclei induced by gastric distension was examined in a freely moving conscious rat model. Physiological levels of gastric distension stimulated the vascular release of 5-HT more than luminal release of 5-HT, and induced c-fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus (PVN), and supraoptic nucleus (SON). The c-fos expression in all these brain nuclei was blocked by truncal vagotomy as well as by perivagal capsaicin treatment, suggesting that vagal afferent pathways may mediate this response. Intravenous injection of 5-HT3 receptor antagonist granisetron blocked c-fos expression in all brain nuclei examined, although intracerebroventricular injection of granisetron had no effect, suggesting that 5-HT released from the stomach may activate 5-HT3 receptors located in the peripheral vagal afferent nerve terminals and then induce brain c-fos expression. c-fos Positive cells in the NTS were labeled with retrograde tracer fluorogold injected in the PVN, suggesting that neurons in the NTS activated by gastric distension project axons to the PVN. The present results suggest that gastric distension stimulates 5-HT release from the EC cells and the released 5-HT may activate 5-HT3 receptors located on the vagal afferent nerve terminals in the gastric wall leading to neuron activation in the NTS and AP and subsequent activation of neurons in the PVN and SON.
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Affiliation(s)
- Takayuki Mazda
- Dept. of Anatomy, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192
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50
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Navarro M, Cubero I. Lateral parabrachial lesions impair lithium chloride-induced aversive responses but not saccharin-induced flavor preference. Brain Res 2003; 990:195-202. [PMID: 14568344 DOI: 10.1016/s0006-8993(03)03530-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Behavioral taste-guided experiments, as well as molecular studies employing c-FLI expression in response to aversive/appetitive unconditioned stimulus, have strongly suggested a visceral role for the lateral parabrachial subnuclei (lPB). The main objective in the present study was to further evaluate the functional role of the lPB in lithium chloride-induced behavioral/physiological responses. We employed a lesion/behavioral experimental strategy combining a lithium chloride-induced place aversion procedure together with the simultaneous evaluation of behavioral ("Lying on Belly", "LOB") and physiological (body temperature) responses elicited by the toxin. Data showed that lPB-lesioned animals failed to avoid the chamber previously paired with lithium chloride. Moreover, "LOB", and not hypothermia, in response to lithium chloride was impaired in parabrachial lesioned animals. Finally, all the animals were tested in a free discriminative flavor-preference task induced by saccharin, a non-caloric reinforcer, which precludes visceral feedback as essential in acquiring the learned response. As expected, both control and lesioned animals developed a clear flavor-preference to the flavor previously paired with saccharin, which shows normal gustatory and associative processing in lPB-lesioned animals. This study extends previous results on the functional visceral role of lPB subnuclei by providing alternative behavioral evidence other than taste-guided behavior, that the lPB is pivotal in visceral processing. Present data are discussed in the context of the visceral hypothesis that holds that the lPB is critically involved in processing post-oral visceral feedback.
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Affiliation(s)
- Montserrat Navarro
- Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, 04120 Almería, Spain
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