Neural Mechanisms that Underlie Eating in the Absence of Hunger

在没有饥饿的情况下进食的神经机制

• 批准号: 10591827
• 负责人: ALEJANDRO RAMIREZ
• 金额: $ 16.7万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-02 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591827
• 关键词: Acute; Amygdaloid structure; Anatomy; Area; Association Learning; Attenuated; Automobile Driving; Behavior; Behavior Therapy; Behavioral Paradigm; Body Weight; Body Weight decreased; Brain; Brain imaging; Calcium; Code; Consumption; Cues; Diet; Eating; Elements; Environment; Exposure to; Feeding behaviors; Food; Foundations; Gene Expression; Goals; Histologic; Histology; Homeostasis; Human; Hunger; Hypothalamic structure; Image; Impairment; Ingestion; Lateral; Learning; Lesion; Mediating; Mus; Nerve; Neuroanatomy; Neurons; Neurosciences; Obesity; Physiological; Population; Prevalence; Primates; Process; Property; Public Health; Rattus; Recombinants; Regulation; Rewards; Rodent Model; Satiation; Sensory; Signal Transduction; Smell Perception; Structure; System; Taste Perception; Techniques; Testing; Time; Training; Viral; Vision; Weight; Weight Gain; bariatric surgery; calcium indicator; craving; dieting; eating in absence of hunger; experimental study; feeding; food consumption; neural; neural circuit; neuromechanism; new therapeutic target; novel therapeutics; obesity development; obesity prevention; obesity treatment; optogenetics; rapid weight gain; response; restoration; sensory stimulus; sound; success; tool

The rising prevalence of obesity throughout the world represents a major public health challenge for the 21st century. Although several new therapies seem likely to be approved, the most effective long-term treatments for obesity are surgical, while current behavioral interventions focused on diet fail 90% of the time. A major challenge in dieting is controlling food intake in the face of our rich sensory environment that includes many sensory cues that have become associated with foods. These sensory cues elicit cravings and food-seeking behavior even in the absence of physiologic need. The amygdala and related brain structures such as orbitofrontal cortex mediate associative learning processes, and the processing of sensory cues in these areas can modulate food consumption. However, the precise neural circuit mechanisms through which cues modulated consumption remain poorly understood, and their interaction with homeostatic signals that limit food intake are completely unknown. Indeed, studying how sensory cues promote feeding in circumstances when homeostatic signals limit consumption has been difficult to study. Here, we propose to study the circuits and mechanism by which sensory cues drive feeding behavior in the absence of hunger, i.e. during acute satiety following a meal and when mice have been overfed to induce hypophagia. We train mice to associate specific sensory cues, e.g. a tone, with rewarding foods, and later use the cue to increase food consumption. We use this behavioral paradigm to test the ability of sensory cues to challenge the return to baseline body weight that occurs following over-feeding, and also to test whether this leads to a higher body weight set-point. We will use state-of-the art neuroscience tools including viral-mediated circuit tracing, activity-dependent recombinant expression of genes, calcium imaging, whole-brain histology, and optogenetics to test the hypothesis that amygdala-related circuits drive cue-induced feeding behaviors via the lateral hypothalamus, and can drive feeding during the absence of hunger. In Aim 1, we will express calcium indicators in amygdala related circuits to study the encoding of sensory stimuli during cue-induced feeding. We then use optogenetics to test whether these areas are necessary and sufficient to modulate cue-induced feeding behaviors. In Aim 2, we will combine cue-induced feeding with overfeeding to test the ability of cue-induced feeding to cause weight gain, and circuit-elements involved in this process. Understanding the neural mechanisms whereby sensory cues can drive feeding-behavior in the absence of physiologic need will help us understand environmental contributors to obesity, and why long-term success in dieting and weight-loss is rare. These studies may ultimately help identify targets for treatment and prevention of obesity.

世界范围内肥胖患病率的上升对人类健康构成了重大挑战