Striatal glutamatergic plasticity and junk-food induced enhancements in cue-triggered food-craving

纹状体谷氨酸可塑性和垃圾食品诱导线索触发的食物渴望增强

• 批准号: 10617336
• 负责人: Carrie Ferrario
• 金额: $ 54.49万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-03 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617336
• 关键词: Address; Adult; Affect; Alzheimer' s Disease; Amygdaloid structure; Behavior; Behavioral; Behavioral Mechanisms; Blinking; Brain; Breeding; Cardiovascular Diseases; Cells; Clinical; Cognitive; Communities; Consumption; Corpus striatum structure; Cues; Data; Development; Diet; Eating; Excision; Exposure to; Female; Food; Foundations; Functional Magnetic Resonance Imaging; Future; Glutamate Receptor; Glutamates; Goals; Health; Human; Link; Malignant Neoplasms; Measures; Medial; Mediating; Metabolic; Metabolic dysfunction; Modeling; Motivation; National Institute of Diabetes and Digestive and Kidney Diseases; Neurobiology; Neurons; Neurophysiology - biologic function; Neurosciences; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Nucleus Accumbens; Obesity; Obesity Epidemic; Permeability; Persons; Physiology; Play; Population; Pre-Clinical Model; Predisposition; Prefrontal Cortex; Prevention strategy; Process; Rat Transgene; Rattus; Reporting; Research; Resistance; Rewards; Role; Signal Transduction; Slice; Smell Perception; Source; Specificity; Strategic Planning; Synaptic Transmission; System; Testing; Transgenic Organisms; United States National Institutes of Health; Weight; Weight Gain; Work; adult obesity; brain behavior; cardiovascular disorder risk; cell type; craving; evidence base; food consumption; food craving; insight; male; motivated behavior; neural; neurobehavioral; novel strategies; obese person; obesity prevention; optogenetics; patch clamp; pharmacologic; pre-clinical; prevent; preventable death; programs; response; sex; therapy development; tool; transmission process; treatment strategy

PROJECT SUMMARY: 40% of U.S. adults are obese. Obesity produces type II diabetes, which increases the risk for cardiovascular disease, many cancers, and Alzheimer's. The NIH strategic plan for obesity research provides “a blueprint (to) encourage the research community to examine the epidemic of obesity from diverse perspectives…in order to develop and evaluate new prevention and treatment strategies”. Further, the NIDDK Cognitive and Clinical Neuroscience of Obesity Program was formed to promote studies of “non-homeostatic brain-behavior mechanisms (to prevent) obesity”. This proposal directly addresses these needs by using novel approaches to understand differences in neural function and behavior in preclinical obesity models. In people, exposure to cues associated with food (food cues), like the smell of brownies or a blinking donuts sign, increases food craving and the amount of food consumed. Obese people report stronger craving and eat larger portions in response to food cues. Further, increases in activity of the nucleus accumbens (NAc) triggered by food cues predict future weight gain inability to lose weight. Thus in people, enhanced neurobehavioral responses to food cues contribute to obesity. But, the mechanism underlying this enhanced neurobehavioral reactivity is unknown. Our long-term goal is to understand the neurobehavioral mechanisms that underlie enhanced cue-triggered `cravings' that contribute to obesity. AMPA type glutamate receptors (AMPAR) provide the main source of excitation to the NAc, and NAc activity is required for cue-triggered motivation in non-obese rats. My lab has found that that cue-triggered food-seeking is stronger in obesity-susceptible males and females prior to obesity and that consumption of a sugary, fatty `junk-food' diet enhances excitatory transmission within the NAc. Our objectives here are to determine the role of NAc glutamatergic plasticity in cue-triggered food-seeking after junk- food exposure, and the degree to which junk-food-induced glutamate plasticity occurs in specific circuits and NAc cell types. These studies address significant gaps in our current understanding of diet-induced plasticity that drives obesity. Our studies will provide key insights into the neural basis of cue-triggered motivation and help delineate behavioral processes and specific circuits involved in both sexes, and as a function of obesity- susceptibility. Eating is often initiated by food cues and eating in response to food cues contributes to human obesity. Thus, this work inform treatment by providing a better understanding of the neurobiological underpinnings of cue-triggered motivation in relevant preclinical models.

项目摘要：40％的美国成年人肥胖。肥胖会产生II型糖尿病，这增加了 患心血管疾病的风险，许多癌症和阿尔茨海默氏症。 NIH肥胖研究战略计划 提供“蓝图（以鼓励研究界）检查潜水员的肥胖症的流行 观点……为了制定和评估新的预防和治疗策略。”此外，NIDDK 形成了肥胖计划的认知和临床神经科学，以促进“非际统治的研究 脑行为机制（预防）肥胖”。该提案直接通过使用新颖的 了解临床前肥胖模型中神经功能和行为差异的方法。在人中 接触与食物（食物提示）相关的提示，例如布朗尼蛋糕的气味或闪烁的甜甜圈标志，增加 食物渴望和食用的食物量。肥胖者报告更渴望和吃更多的部分 对食物提示的反应。此外，食物提示触发的伏隔核（NAC）的活性增加 预测未来的体重增加无法减肥。在人们中，神经行为对食物的反应增强 提示有助于肥胖。但是，这种增强的神经行为反应性的基础机制尚不清楚。 我们的长期目标是了解增强的提示触发的神经行为机制 有助于肥胖的“渴望”。 AMPA型谷氨酸接收器（AMPAR）提供了主要来源 对NAC的激发和NAC活性是非肥胖大鼠提示动机所必需的。我的实验室有 发现在肥胖之前，肥胖抑制的雄性和女性在肥胖之前，寻求食物的寻求食物更强 含糖，脂肪“垃圾食品”饮食的消费增强了NAC内的兴奋性传播。我们的 这里的目的是确定NAC谷氨酸能可塑性在垃圾后在提示触发的寻求食物中的作用 食物暴露，以及垃圾食品诱导的谷氨酸可塑性在特定电路中发生的程度和 NAC细胞类型。这些研究解决了我们当前对饮食诱导可塑性的理解的显着差距 这驱动了肥胖。我们的研究将提供有关提示触发动机的神经基础的关键见解和 帮助描述两性涉及的行为过程和特定电路，并取决于肥胖的函数 - 敏感性。饮食通常是由食物提示引发的，而饮食则响应食物提示会导致人类 肥胖。这是通过更好地理解神经生物学来为治疗提供信息的 相关临床前模型中，提示触发动机的基础。