Parabrachial-Forebrain Interactions in CTA

CTA 中臂旁前脑相互作用

• 批准号: 6851798
• 负责人: STEPHEN REILLY
• 金额: $ 28.15万
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6851798
• 关键词: association learning; avoidance behavior; behavior test; behavioral /social science research tag; brain mapping; central neural pathway /tract; conditioning; intercellular connection; laboratory rat; neural information processing; parabrachial nucleus; prosencephalon; taste

DESCRIPTION (provided by applicant): The long term goal of the current proposal is to determine the neural substrates of conditioned taste aversion (CTA), a profoundly important learning mechanism that protects against the repeated ingestion of toxic food. Evolution has predisposed animals (including humans) to associate gastrointestinal malaise (termed the unconditioned stimulus or US) with the taste of the food (the conditioned stimulus or CS). So powerful is this mechanism that cancer patients (despite the fact that they are fully aware that the food did not cause the illness) may develop strong aversions to their diets (leading to a loss of appetite and anorexia) because the adverse visceral side effects of chemotherapy are nonetheless associated with the foods they consumed before treatment. Similarly, animals rendered comatose following consumption of food nevertheless display a CTA if they survive the poisoning. These and related findings emphasize the importance of brainstem nuclei in the development of CTAs. We have helped identify the medial parabrachial nucleus (MPBN) as a fundamentally important area for the acquisition of CTA. We consider that the MPBN is critically involved in the associative mechanism that links the taste CS with the aversive US. However, the finding that chronic precollicular decerebrations (which disconnect the brainstem from the forebrain while leaving the MPBN intact) also prevent the acquisition of CTA, indicates that the MPBN does not work alone: CTA acquisition depends upon an interplay between the MPBN and forebrain structures. Thus, the present proposal seeks answers to the following questions: (1) which forebrain structures interact with the MPBN during CTA acquisition and (2) what is the nature of that interaction? Specific Aim 1 will address the first question by focusing on five brain regions that are connected with the MPBN and, in most cases, have been implicated in some aspect of CTA: the basolateral arnygdala, central nucleus of the amygdala, insular cortex, lateral hypothalamus and the bed nucleus of the stria terminalis. To determine the nature of the MPBN-forebrain interactions, Specific Aims 2 and 3 will employ tasks that have previously proven successful in identifying the role of the MPBN in CTA. By studying the behavioral breakdowns consequent to excitotoxic lesions of structures connected with the MPBN, we expect to make significant progress in our long-term goal of defining the neural system responsible for CTA acquisition.

描述（由申请人提供）：当前提案的长期目标是确定条件味觉厌恶（CTA）的神经底物，这是一种非常重要的学习机制，可防止反复摄入有毒食物。进化具有诱人的动物（包括人类），以将胃肠道不适（称为无条件刺激或美国）与食物的味道（条件刺激或CS）联系起来。这种机制是如此强大，以至于癌症患者（尽管他们完全意识到食物并没有引起疾病）可能会对饮食产生强烈的厌恶（导致食欲和厌食症的丧失），因为化学疗法的不良内脏副作用与治疗前消耗的食物相关。同样，如果动物消耗食物后，如果动物在中毒中幸存下来，就会显示出CTA。这些和相关的发现强调了脑干核对CTA的发展的重要性。我们已经帮助确定内侧止痛核（MPBN）是获得CTA的根本重要领域。我们认为，MPBN与将口味CS与厌恶的美国联系起来的关联机制非常重要。然而，发现慢性前结发（在离开MPBN完整的同时使脑干与前脑断开脑干的连接）也可以阻止CTA的获取，这表明MPBN不单独使用：CTA的习惯取决于MPBN和前脑结构之间的互动。因此，本提案寻求以下问题的答案：（1）在CTA获取过程中，哪些前脑结构与MPBN相互作用，以及（2）这种相互作用的本质是什么？具体目标1将通过关注与MPBN相关的五个大脑区域来解决第一个问题，并且在大多数情况下，与CTA的某些方面有关：基底外侧Arnygdala，杏仁核的中央核，独立的皮质，独立的皮质，侧丘脑，下丘脑下丘脑和Stria sucleus的床核。为了确定MPBN-前脑相互作用的性质，具体目的2和3将采用以前证明成功地确定MPBN在CTA中的作用的任务。通过研究与MPBN相关的结构的兴奋性病变所致的行为崩溃，我们希望在定义负责CTA获取的神经系统的长期目标中取得重大进展。