Parabrachial-Forebrain Interactions in Conditioned Taste Aversion

条件性味觉厌恶中的臂旁前脑相互作用

• 批准号: 8037154
• 负责人: STEPHEN REILLY
• 金额: $ 28.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8037154
• 关键词: Adverse effects; Amygdaloid structure; Animal Feed; Animals; Anorexia; Attenuated; Behavioral; Brain; Brain Stem; Cachexia; Cancer Patient; Cause of Death; Cell Nucleus; Chronic; Coma; Data; Decerebration procedure; Development; Diet; Eating; Evolution; Familiarity; Feeding behaviors; Food; Foundations; Glutamate Receptor; Glutamates; Goals; Human; Infusion procedures; Ingestion; Intervention; Laboratories; Lead; Learning; Lesion; Life; Malaise; Medial; Medical; Memory; Neurons; Nutritional; Perception; Pharmaceutical Preparations; Plastics; Poisoning; Procedures; Process; Prosencephalon; Protein Biosynthesis; Protein Synthesis Inhibition; Rattus; Research; Retrieval; Role; Site; Structure; System; Taste Perception; Visceral; cancer radiation therapy; chemotherapy; food consumption; functional loss; gastrointestinal; insight; novel; parabrachial nucleus; prevent; public health relevance; relating to nervous system; research study; therapy development

DESCRIPTION (provided by applicant): Faced with a novel food, an animal is confronted with a decision that cannot be taken lightly. While ingestion of the food may lead to a nutritious meal, it may, if the food is poisonous, cause death. Powerful learning processes have evolved to guide ingestive behavior. The most important of these processes, conditioned taste aversion (CTA) learning, not only prevents the repeated ingestion of toxic food, and therefore has wide reaching implications for dietary choices in everyday life, but also is implicated in many other situations relevant to our well being. For instance, cancer patients oftentimes develop strong aversions to their diets (leading to anorexia and cachexia) because the aversive visceral side effects of chemotherapy are associated with the foods consumed before treatment. Our research encourages the view that the absence of CTA in chronic decerebrate rats is the inadvertent consequence of a decerebration-induced functional loss of neurons in the parabrachial nucleus (PBN). Indeed, we believe that the PBN is the single most important brain structure for CTA learning and that the forebrain contributes to the PBN associative mechanism by modulating the perception of taste novelty/familiarity. The goals of the proposed research are to: (1) determine the pharmacological substrates of CTA learning in the PBN and (2) establish the roles of forebrain structures in taste novelty perception. The research of our first goal utilizes intraPBN drug infusions to determine whether CTA acquisition and/or reconsolidation is a protein synthesis- (Specific Aim 1) and/or a glutamate receptor- (Specific Aim 2) dependent process in the PBN. The research of our second short-term goal will investigate the roles of forebrain structures (insular cortex, basolateral amygdala and medial amygdala) in a novelty recognition procedure (taste neophobia) using a disconnection strategy involving asymmetric lesions (Specific Aim 3) or temporary inactivation (Specific Aim 4). By studying the behavioral breakdowns consequent to the stated brain manipulations, we expect to make significant progress in our long-term goal of defining the neural system responsible for CTA learning. PUBLIC HEALTH RELEVANCE: Conditioned taste aversions (CTAs), which are rapidly acquired when ingestion of a novel food is followed by gastrointestinal malaise, are manifest as a diminished intake of that food on subsequent encounters. Understanding the neural substrates of this profoundly important learning process will yield insights into the neural integration of gustatory and visceral functions and may provide a foundation for the development of treatments and interventions that might ameliorate, for example, the unwanted, and oftentimes debilitating, nutritional side effects of invasive medical therapies such as chemo- or radiation therapy for cancer.

描述（由申请人提供）：面对一种新食物，动物面临着不能轻易做出的决定。虽然食物摄入可能会导致营养餐，但如果食物有毒，可能会导致死亡。强大的学习过程已经演变为指导摄入行为。这些过程中最重要的是条件味道厌恶（CTA）学习，不仅可以防止反复摄入有毒食品，因此对日常生活中的饮食选择具有广泛的影响，而且还与许多其他与我们的健康相关的情况有所帮助。例如，由于化学疗法的厌恶性内脏副作用与治疗前消耗的食物有关，因此癌症患者通常会对饮食产生强烈的厌恶（导致厌食症和恶病质）。我们的研究鼓励这样一种观点，即慢性杂脑大鼠缺乏CTA是副核核（PBN）中神经元的功能丧失的无意后果。确实，我们认为PBN是CTA学习的最重要的大脑结构，而前脑则通过调节对味觉新颖性/熟悉度的感知来促进PBN关联机制。拟议的研究的目标是：（1）确定PBN中CTA学习的药理底物，（2）确定前脑结构在味觉新颖性感知中的作用。对我们的第一个目标的研究利用IntrapBN药物输注来确定CTA获取和/或重新溶解是否是蛋白质合成的 - PBN中PBN中的蛋白质合成（特定目标1）和/或谷氨酸受体（特定目标2）依赖性过程。我们第二个短期目标的研究将研究前脑结构（岛状皮层，基底外侧杏仁核和内侧杏仁核）在新颖的识别程序（味觉新恐惧症）中使用涉及非对称病变（特定目标3）或临时灭活（特定目标4）的新颖性识别程序（味觉新恐惧症）。通过研究针对既定的大脑操纵的行为崩溃，我们希望在定义负责CTA学习的神经系统的长期目标中取得重大进展。 公共卫生相关性：条件味道厌恶（CTA），当摄入新食物之后是胃肠道不适时会迅速获得，这表现为在随后的相遇中摄入的食物降低。了解这一极为重要的学习过程的神经底物将产生对糖和内脏功能的神经整合的见解，并可能为开发治疗和干预措施的发展提供基础，这些疗法和干预措施可能会改善，例如，不必要的和令人衰弱的衰弱，令人衰弱的，诸如Chepiation医学治疗的营养副作用，例如化学治疗或Hartiatien或Hartiation Chance cancer的癌症。