Parabrachial-Forebrain Interactions in Conditioned Taste Aversion

描述(申请人提供)：面对一种新奇的食物，动物面临着一个不能掉以轻心的决定。虽然摄入这种食物可能会导致营养丰富的一餐，但如果食物有毒，它可能会导致死亡。强大的学习过程已经演变成指导进食行为。其中最重要的过程，条件性厌恶味觉(CTA)学习，不仅可以防止重复摄入有毒食物，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关。例如，癌症患者经常对他们的饮食产生强烈的反感(导致厌食症和恶病质)，因为化疗的不良内脏副作用与治疗前摄入的食物有关。我们的研究支持这样一种观点，即慢性去大脑大鼠缺乏CTA是去大脑导致臂旁核(PBN)神经元功能丧失的无意后果。事实上，我们认为，PBN是CTA学习最重要的大脑结构，前脑通过调节对味道新鲜度/熟悉度的感知而对PBN联想机制做出贡献。本研究的目标是：(1)确定外周核内CTA学习的药理学基础；(2)确定前脑结构在味觉新奇知觉中的作用。我们第一个目标的研究利用PBN内注射药物来确定CTA的获得和/或再巩固是否是PBN中的蛋白质合成(特异性目标1)和/或谷氨酸受体(特异性目标2)依赖的过程。我们的第二个短期目标的研究将调查前脑结构(岛叶皮质、杏仁基底外侧核和杏仁内侧核)在新奇识别过程(味觉新恐惧症)中的作用，使用涉及不对称病变(特定目标3)或暂时失活(特定目标4)的断开策略。通过研究上述大脑操作导致的行为障碍，我们希望在定义负责CTA学习的神经系统的长期目标方面取得重大进展。

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.