Functional and Behavioral Characterization of Central Amygdala Glucagon Like Peptode-1 Receptors

中央杏仁核胰高血糖素样 Peptode-1 受体的功能和行为特征

基本信息

项目摘要

Project Summary Drugs that target the glucagon-like peptide 1 receptor (GLP-1R) system are commonly prescribed for the treatment of type II diabetes. Unfortunately, we do not yet fully understand how these drugs work on targets in the central nervous system or how brain GLP-1Rs regulate eating behaviors. In this proposal we will characterize the functional role of GLP-1Rs in the central amygdala (CeA) using neural circuit, genetic, and behavioral approaches in laboratory mice. In Aim 1, we will use fiber photometry of GCaMP7 in the CeA in combination with 1) local deletion of CeA GLP-1 and 2) local CeA administration of GLP-1R agonists to determine the functional role of CeA GLP-1Rs in regulating neural activity and neural responses to peripherally applied GLP-1R agonists. In Aim 2, we will use site-specific genetic deletion of CeA GLP-1Rs in combination with high precision, longitudinal assessment of feeding using miniaturized feeding devices that can be used in the mouse homecage and adapted for operant feeding. Using this technology, we will measure appetitive and consummatory behavior under free or operant conditions throughout the light cycle over several weeks. We will also determine if CeA GLP-1Rs are required for the anorexigenic effects of peripherally administered GLP-1R agonists using two separate paradigms: fasting-induced refeed and intermittent access to high fat diet. Using these two binge-like eating paradigms will peripherally administer Exendin-4, a potent GLP-1R agonist, in the presence or absence of CeA GLP-1Rs. We hypothesize that CeA GLP-1Rs are required for the neurophysiological effects of peripherally administered GLP-1R agonists on the CeA and that activation of CeA GLP-1Rs is sufficient to induce robust changes in CeA neural activity in vivo. Behaviorally, we hypothesize that CeA GLP-1Rs constrain motivation and appetitive behavior for palatable food, and that deletion of these receptors will partially suppress the effects of peripheral GLP-1R agonists on binge-like food intake. Over the long-term we hope to understand the contribution of the brain’s endogenous GLP-1R system that may inform more effective treatments for obesity and type II diabetes.
项目总结

项目成果

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James Andrew Hardaway其他文献

James Andrew Hardaway的其他文献

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{{ truncateString('James Andrew Hardaway', 18)}}的其他基金

Functional and Behavioral Characterization of Central Amygdala Glucagon Like Peptode-1 Receptors
中央杏仁核胰高血糖素样 Peptode-1 受体的功能和行为特征
  • 批准号:
    10286169
  • 财政年份:
    2021
  • 资助金额:
    $ 11.14万
  • 项目类别:
Functional and Behavioral Characterization of Central Amygdala Glucagon Like Peptode-1 Receptors
中央杏仁核胰高血糖素样 Peptode-1 受体的功能和行为特征
  • 批准号:
    10414577
  • 财政年份:
    2021
  • 资助金额:
    $ 11.14万
  • 项目类别:
Functional and Behavioral Characterization of Central Amygdala Glucagon Like Peptode-1 Receptors
中央杏仁核胰高血糖素样 Peptode-1 受体的功能和行为特征
  • 批准号:
    10502881
  • 财政年份:
    2021
  • 资助金额:
    $ 11.14万
  • 项目类别:
A Nociceptin Central Amygdala to Hindbrain Circuit for the Control of Palatable Food Consumption
用于控制可口食物消耗的伤害感受肽中央杏仁核到后脑回路
  • 批准号:
    10103903
  • 财政年份:
    2020
  • 资助金额:
    $ 11.14万
  • 项目类别:
A Nociceptin Central Amygdala to Hindbrain Circuit for the Control of Palatable Food Consumption
用于控制可口食物消耗的伤害感受肽中央杏仁核到后脑回路
  • 批准号:
    10413010
  • 财政年份:
    2020
  • 资助金额:
    $ 11.14万
  • 项目类别:
A Nociceptin Central Amygdala to Hindbrain Circuit for the Control of Palatable Food Consumption
用于控制可口食物消耗的伤害感受肽中央杏仁核到后脑回路
  • 批准号:
    10159256
  • 财政年份:
    2020
  • 资助金额:
    $ 11.14万
  • 项目类别:
Presynaptic Mechanisms Regulating the Dopamine Transporter
调节多巴胺转运蛋白的突触前机制
  • 批准号:
    8207320
  • 财政年份:
    2010
  • 资助金额:
    $ 11.14万
  • 项目类别:
Presynaptic Mechanisms Regulating the Dopamine Transporter
调节多巴胺转运蛋白的突触前机制
  • 批准号:
    8061759
  • 财政年份:
    2010
  • 资助金额:
    $ 11.14万
  • 项目类别:
Presynaptic Mechanisms Regulating the Dopamine Transporter
调节多巴胺转运蛋白的突触前机制
  • 批准号:
    8387035
  • 财政年份:
    2010
  • 资助金额:
    $ 11.14万
  • 项目类别:

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